We examined the hepatoprotective activity of Inonotus obliquus water extract (IO-W) against tert-butyl hydroperoxide (t-BHP)-induced oxidative liver injury in the primary cultured rat hepatocyte. The 50% radical scavenging concentrations (SC50s) of IO-W for radical-scavenging activity against 2,2'-azino-bis-(3-ethylbenzothi- azoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) were 5.19 mg/mL and 0.39 mg/mL, respectively. IO-W pretreatment to the primary cultured hepatocytes significantly (p<0.05) protected the cells from t-BHP-induced cytotoxic injury even at a low concentration of IO-W (10µg/mL). The cellular leakage of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH), as well as malondialdehyde (MDA) formation caused by t-BHP were significantly (p<0.05) suppressed by IO-W pretreatment (>100µg/ mL). In conclusion, this study demonstrates that IO-W exhibited hepatoprotective activity against t-BHP-induced oxidative liver injury in the primary cultured hepatocyte probably via its abilities of quenching free radicals, inhibiting the leakage of ALT, AST, and LDH, and decreasing MDA formation.

Prevention and restoration of hepatic fibrosis from chronic liver injury is essential for the treatment of patients with chronic liver diseases. Vitamin C is known to have hepatoprotective effects, but their underlying mechanisms are unclear, especially those associated with hepatic fibrosis. Here, we analyzed the impact of vitamin C on bile acid induced hepatocyte apoptosis in vitro and lithocholic acid (LCA)-induced liver injury in vitamin C-insufficient Gulo(-/-) mice, which cannot synthesize vitamin C similarly to humans. When Huh-BAT cells were treated with bile acid, apoptosis was induced by endoplasmic reticulum stress-related JNK activation but vitamin C attenuated bile acid-induced hepatocyte apoptosis in vitro. In our in vivo experiments, LCA feeding increased plasma marker of cholestasis and resulted in more extensive liver damage and hepatic fibrosis by more prominent apoptotic cell death and recruiting more intrahepatic inflammatory CD11b(+) cells in the liver of vitamin C-insufficient Gulo(-/-) mice compared to wild type mice which have minimal hepatic fibrosis. However, when vitamin C was supplemented to vitamin C-insufficient Gulo(-/-) mice, hepatic fibrosis was significantly attenuated in the liver of vitamin C-sufficient Gulo(-/-) mice like in wild type mice and this hepatoprotective effect of vitamin C was thought to be associated with both decreased hepatic apoptosis and necrosis. These results suggested that vitamin C had hepatoprotective effect against cholestatic liver injury.

BACKGROUND & AIMS:Dietary modification has been recommended for treatment of nonalcoholic fatty liver disease (NAFLD), although it is not clear whether improving diet quality can prevent its development. We performed a prospective study to examine the association between diet quality change and change in liver fat change. We also examined the association between genetic risk score and liver fat change in individuals with different levels of diet quality change.

METHODS:Our study included 1521 participants who attended the seventh and eighth examinations (1998-2001 and 2005-2008) of the second-generation cohort or attended the first and second examinations (2002-2005 and 2008-2011) of the third-generation cohort in the Framingham Heart Study. The self-administered semi-quantitative 126-item Harvard food frequency questionnaire was used to determine dietary intake in the year leading up to an examination. We assessed levels of liver fat using liver-phantom ratio (LPR) and computed tomography images from 2002 through 2005 and again from 2008 through 2011. LPR values are inversely related to liver fat-increased LPR indicates decreased liver fat. We examined associations of changes in 2 diet scores-the Mediterranean-style diet score (MDS) and Alternative Healthy Eating Index (AHEI)-with changes in liver fat and new-onset fatty liver. We evaluated interactions between diet score change and a weighted genetic risk score for NAFLD, determined based on multiple single nucleotide polymorphisms identified in genome-wide association studies of NAFLD. The primary outcome was change in LPR between baseline and follow-up measurement.

RESULTS:For each 1-standard deviation increase in MDS, the LPR increased (meaning liver fat decreased) by 0.57 (95% CI, 0.27-0.86; P<.001) and the odds for incident fatty liver decreased by 26% (95% CI, 10%-39%; P=.002). For each 1-standard deviation increase in AHEI, LPR increased by 0.56 (95% CI, 0.29-0.84; P<.001) and the odds for incident fatty liver decreased by 21% (95% CI, 5%-35%; P=.02). Increased diet scores were also associated with reduced odds of developing more-advanced fatty liver. Higher genetic risk scores were associated with increased liver fat accumulation in participants who had decreased MDS (P<.001) or AHEI scores (P=.001), but not in those with stable or improved diet scores (P for gene-diet interaction<.001).

CONCLUSIONS:In an analysis of participants in the Framingham Heart Study, increasing diet quality, determined based on MDS and AHEI scores, is associated with less liver fat accumulation and reduced risk for new-onset fatty liver. An improved diet is particularly important for individuals with a high genetic risk for NAFLD.

AIM:l-ascorbic acid (vitamin C) insufficiency is considered one of the major risk factors for the development of liver disease. However, its specific effects and related mechanisms in vivo are largely unknown. The objective of this study was to investigate the in vivo protective role of vitamin C and its related mechanisms in liver injury with Gulo(-/-) mice that cannot synthesize vitamin C like humans due to the lack of l-gulonolactone-γ-oxidase (Gulo), an essential enzyme for vitamin C synthesis.

RESULTS:When liver injury was induced in Gulo(-/-) mice by injection of concanavalin A (Con A), there was greater extensive liver damage accompanied by an increased number of apoptotic hepatocytes in vitamin C-insufficient Gulo(-/-) mice. Additionally, the plasma and hepatic levels of the proinflammatory cytokines, such as TNF-α and IFN-γ, were much higher in the vitamin C-insufficient Gulo(-/-) mice than in the control mice. Moreover, increased numbers of liver-infiltrating T-cells in the vitamin C-insufficient Gulo(-/-) mice were related to the increased hepatic levels of IFN-inducible factor (IP-10). Although the vitamin C-insufficient Gulo(-/-) mice had higher amounts of interleukin-22 (IL-22), a hepatoprotective cytokine, a defect in IL-22Rα expression and its downstream STAT3 activation in hepatocytes were found.

INNOVATION:We first demonstrate the novel in vivo action mechanisms of vitamin C on the prevention of disease development in the liver, through the regulation of excessive immune activation and maintenance of the IL-22Rα signaling pathways.

CONCLUSION:These results suggest that severe liver damage induced by inflammation could be prevented by sufficient supplementation with vitamin C.

Background and objectives:Nonalcoholic steatohepatitis (NASH) is strongly associated with obesity. A weight loss of≥10% is necessary to improve NASH severity, but this goal has rarely been achieved in published studies using different diet protocols. The effect of a ketogenic, hypocaloric, commercial diet ("Ideal Protein,"IP) on body weight, metabolic markers, and liver tests in a group of NASH patients is evaluated in this study. Daily calorie intake was tailored to achieve a weight loss of≥10%.

Methods:We analyzed 38 patients with NASH who were placed on the IP diet between 2014 and 2018 and compared their outcomes with 6 control patients who declined the diet. All patients were evaluated by a trained health coach in weekly intervals throughout the study period. Clinical and laboratory data obtained before and at 6.5 months after intervention were compared using paired t-testing.

Results:The patients on the IP diet experienced a significant weight reduction (217± 8 lb. 194± 7 lb; mean ± S.E.M.), corresponding to an average weight loss of 9.7% ± 1.6%. Significant changes in systolic blood pressure (133 ± 3 mmHg. 123± 3 mmHg), triglycerides (200 ± 21 mmol/L. 132± 11 mmol/L), hemoglobin A1c (6.71% ± 0.29%. 5.74%± 0.19%), SGPT (97.3 ± 11.1 IU/L. 44.2± 5.9 IU/L), SGOT (82.4 ± 10.5 IU/L. 32.8± 5.2 IU/L), and Fib-4 scores (2.25 ± 0.23. 1.40± 0.13) were also observed (<0.05 in all cases). In the IP group, 50.5% of patients lost≥10% body weight. In contrast, no significant changes were observed in the control group. The IP diet was well tolerated, and no safety signals were noticed.

Conclusions:A ketogenic, hypocaloric resulted in striking weight loss and significant improvements in metabolic parameters and liver tests, suggesting that this approach carries promise for the dietary management of patients with NASH.

Nutritional habits modifications have shown an important impact in preventing and ameliorating metabolic alterations, such as nonalcoholic fatty liver disease (NAFLD). Among several dietary approaches that exert positive effects in NAFLD patients, the Mediterranean dietary pattern has shown notable benefits. This review explores the molecular mechanisms through which the Mediterranean diet would improve risk factors associated with metabolic syndrome and NAFLD. The main features of the Mediterranean diet acting on metabolism are represented by its whole-grain and low glycemic index cereal-based items, its fatty acid profile, and its content in phytochemical compounds. Carbohydrate-rich foods high in dietary fiber inducing low glycemic response are able to interact with glucose and insulin metabolism. Unsaturated fatty acids are associated with better hepatic lipid metabolism. Finally, phytochemical compounds, such as dietary polyphenols, are thought to ameliorate inflammation, which is considered one of the mechanisms through which NALFD may evolve into nonalcoholic steatohepatitis (NASH).

We have shown that combination treatment with decaffeinated green tea extract (GTE) and voluntary exercise (Ex) reduces obesity and insulin resistance in high-fat (HF)-fed mice to a greater extent than either treatment alone. Here, we investigated the effects of GTE-, Ex- or the combination on the development of obesity-related NAFLD. Male C57BL/6 J mice were treated for 16 weeks with HF diet (60% energy from fat), HF supplemented with 7.7 g GTE/kg, HF plus access to a voluntary running wheel, or the combination. We found that treatment of mice with the combination mitigated the development of HF-induced NAFLD to a greater extent than either treatment alone. Combination-treated mice had lower plasma alanine aminotransferase (92% lower) and hepatic lipid accumulation (80% lower) than HF-fed controls: the effect of the single treatments was less significant. Mitigation of NAFLD was associated with higher fecal lipid and nitrogen levels. Combination treated, but not singly treated mice, had higher hepatic expression of genes related to mitochondrial biogenesis (sirtuin 1 [59%]; peroxisome proliferator-activated receptorγ coactivator 1α [42%]; nuclear respiratory factor 1 [38%]; and transcription factor B1, mitochondrial [89%]) compared to the HF-fed controls. GTE-, Ex-, and the combination-treatment groups also had higher hepatic expression of genes related to cholesterol synthesis and uptake, but the combination was not better than the single treatments. Our results suggest the combination of GTE and Ex can effectively mitigate NAFLD. Future studies should determine if the combination is additive or synergistic compared to the single treatments.

Nonalcoholic fatty liver disease (NAFLD) develops in ulcerative colitis (UC) and Crohn's disease. However, there is scarce reporting on the onset of UC in patients with NAFLD. A 44-year-old man was diagnosed with UC and referred to us in 2019. His height was 166.0 cm, and body weight was 86.3 kg. The waist circumference was 93.7 cm (normal range<85) and triglyceride was 751 mg/dL. These findings, in addition to hypertension, resulted in a diagnosis of metabolic syndrome. HbA1c was normal. Ultrasonography disclosed severe fatty liver. Nonalcoholic fatty liver disease was diagnosed. He underwent 12 days of educational hospitalization for UC. A lacto-ovo-semi-vegetarian diet (1400 kcal/day), a kind of plant-based diet (PBD), was provided. He lost 4 kg, which was 4.6% of his base body weight. Triglyceride and total cholesterol decreased to the normal ranges. Transaminases andγ-glutamyl transpeptidase also decreased. His body weight decreased further after discharge. Follow-up ultrasonography indicated an improvement in hepatic enlargement. The shear wave velocity decreased from 1.11 to 0.88 m/s. His soft stool became normal stool by 2 months after discharge. Records ofhis health checkups revealed the presence of metabolic syndrome and abnormal liver function tests already in 2015. Thus, it was concluded that UC developed in a patient with NAFLD in this case. Plant-based diet has already been shown to be effective in inflammatory bowel disease (IBD). In the present case, NAFLD parameters were dramatically improved by PBD. Whether the improvement was due to weight loss per se or due to weight loss with PBD is to be clarified.

BACKGROUND:Lead toxicity is a public health concern. Lead is one of the dispensable and non-biodegradable heavy metals and is toxic even at low concentrations.

OBJECTIVE:This study was to investigate the effect of oral administration of Vitamin C and Vitamin E on lead-induced hepatotoxicity and oxidative stress in the brain of rats.

METHODS:Thirty Sprague-Dawley albino male albino rats (115.58 +/- 4.96g) were divided equally into five groups. The rats were fed rat chow and water ad libitum. Group 1 rats served as control and were orally administered 2ml saline every day for 7 weeks. Group 2 rats received orally 2ml lead acetate solution (60mg/kg body weight) every day for 7 weeks. Group3 rats received orally 2ml lead acetate solution (60mg/kg body weight) and vitamin C (40mg/kg body weight) every other day for 7 weeks. Group 4 rats received orally 2ml lead acetate solution (60mg/kg body weight) and vitamin E (150mg/kg body weight)every day for 7weeks. Group 5 received orally lead acetate solution at 60mg/kg body weight and vitamin C (40mg/kg body weight)and vitamin E (150mg/kg body weight) every other day for 7weeks. Three rats from each group were sacrificed after the fourth week. The remaining rats were sacrificed after the seventh week. Changes in body weight, liver weight, brain weight, activities of liver function enzymes (aspartate amino transferase (AST), alanine amino transferase (ALT) and alkaline phosphatase(ALP) in the serum at week 4 and week 7 were assayed.The oxidative stress markers (reduced glutathione (GSH), nitric oxide(NO), malondialdehyde(MDA), levels, catalase(CAT) and superoxide dismutase (SOD) activities) were determined in the brain of rats. Serum lead level of rats was also determined.

RESULTS:The lead Pb exposed rats caused a significant (p<0.01) increase in bioavailable lead in the blood (p<0.05) as compared to the control. AST, ALT and ALPactivities were significantly increased (p<0.05) in the serum of rats exposed to lead as compared to the control. NO and MDA levels were significantly increased (p<0.05) in the brain of rats exposed to lead, while GSH level, SOD and CAT activities were significantly reduced (p<0.05) in the brain of rats exposed to lead when compared with the control.

CONCLUSION:Data of the study indicate that oral administration of vitamin C and vitamin E significantly reduced the blood lead concentration, ameliorates the hepatic damage and significantly reduced the oxidative stress in the brain of rats.

Nicotine is a potential inducer of oxidative stress, through which it can damage numerous biological molecules. The aim of our study was to investigate the prooxidative effects of nicotine and protective (additive or synergistic) effects of quercetin and vitamin C in the blood of experimental animals, to determine whether the combination of these antioxidants might be beneficial for clinical purposes. Wistar albino rats were receiving intraperitoneal nicotine injection (0.75 mg kg-1 per day) or saline (control group) or nicotine plus quercetin (40 mg kg-1 per day) and vitamin C (100 mg kg-1 per day) for three consecutive days. On day 4, we determined their blood lipid profile, liver enzymes, oxidative stress parameters, and antioxidative system parameters. Compared to untreated control, nicotine significantly increased total cholesterol, LDLcholesterol, triglycerides, liver enzymes (alanine transaminase, aspartate transaminase, and lactate dehydrogenase) and oxidative stress parameters (superoxide anion, hydrogen peroxide, and lipid peroxide) and decreased HDL-cholesterol, glutathione, and superoxide dismutase/catalase activity. Quercetin + vitamin C reversed these values significantly compared to the nicotine alone group. Our results confirm that nicotine has significant prooxidative effects that may disrupt the redox balance and show that the quercetin + vitamin C combination supports antioxidant defence mechanisms with strong haematoprotective activity against nicotine-induced toxicity. In practical terms, this means that a diet rich in vitamin C and quercetin could prevent nicotine-induced toxicity and could also be useful in the supportive care of people exposed to nicotine.

ETHNOPHARMACOLOGICAL RELEVANCE:Sports anemia is a persistent and severe problem in athletes owing to strenuous exercise-induced oxidative stress and hepcidin upregulation. The roots of Angelica sinensis (AS), a familiar traditional Chinese medicine, has been used for replenishing blood since antiquity.

AIM OF THE STUDY:To evaluate the effects of ethanolic AS extract in a 4-week study on sports anemia in female Wistar rats.

MATERIALS AND METHODS:To induce anemia, a strenuous exercise protocol consisting of running and swimming was employed with increasing intensity. Animals were randomly assigned to the following groups: control group; strenuous exercise group; and strenuous exercise and AS extract-treated group (300mgkg(-1)d(-1)). After 4 weeks, rats underwent exhaustive swimming and forelimb grip strength test. The blood biochemical markers and hepatic antioxidant activities were determined. Hepatic interleukin-6 and muscle glycogen were observed through immunohistochemical and Periodic acid-Schiff staining, respectively.

RESULTS:AS extract (consisting of ferulic acid, Z-ligustilide, and n-butylidenephthalide) treatment improved forelimb grip strength and rescued exercise-induced anemia by significantly elevating the red blood cell counts and hemoglobin concentrations as well as hematocrit levels (p<0.05). AS modulated the iron metabolism through decreasing serum hepcidin-25 concentrations by 33.0% (p<0.05) and increasing serum iron levels by 34.3% (p<0.01). The hepatic injury marker serum alanine aminotransferase concentrations were also reduced, followed by increased antioxidant enzyme catalase expression in the liver (p<0.05). Furthermore, substantial attenuation of hepatic interleukin-6 expression and preservation of muscle glycogen content suggested the additional roles of AS acting on sports anemia and physical performance.

CONCLUSION:Our findings evidenced a novel and promising therapeutic approach for AS treatment for rescuing the anemic condition induced following 4 weeks of strenuous exercise.

Hepatic disorders such as steatosis and alcoholic steatohepatitis are common diseases that affect thousands of people around the globe. This study aims to identify the main phenol compounds using a new HPLC-ESI+-MS/MS method, to evaluate some oxidative stress parameters and the hepatoprotective action of green dwarf coconut water, caffeic and ascorbic acids on the liver and serum of rats treated with ethanol. The results showed five polyphenols in the lyophilized coconut water spiked with standards: chlorogenic acid (0.18µM), caffeic acid (1.1 µM), methyl caffeate (0.03 µM), quercetin (0.08 µM) and ferulic acid (0.02 µM) isomers. In the animals, the activity of the serum γ-glutamyltranspeptidase (γ-GT) was reduced to 1.8 I.U/L in the coconut water group, 3.6 I.U/L in the ascorbic acid group and 2.9 I.U/L in the caffeic acid groups, when compared with the ethanol group (5.1 I.U/L, p<0.05). Still in liver, the DNA analysis demonstrated a decrease of oxidized bases compared to ethanol group of 36.2% and 48.0% for pretreated and post treated coconut water group respectively, 42.5% for the caffeic acid group, and 34.5% for the ascorbic acid group. The ascorbic acid was efficient in inhibiting the thiobarbituric acid reactive substances (TBARS) in the liver by 16.5% in comparison with the ethanol group. These data indicate that the green dwarf coconut water, caffeic and ascorbic acids have antioxidant, hepatoprotective and reduced DNA damage properties, thus decreasing the oxidative stress induced by ethanol metabolism.

The aim of this work was designed to investigate the antioxidant, antiaging, and hepatoprotective effects of alkali-extractable polysaccharides (AlAPS) and their three purified fractions (AlAPS-1, AlAPS-2, and AlAPS-3) fromin D-galactose induced aging mice. Forantioxidant analysis, both AlAPS and its fractions exhibited moderate reducing power, Fe-chelating activities, and potent scavenging activities on hydroxyl and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. Theresults demonstrated that the polysaccharides, especially AlAPS-2, showed potential antiaging and hepatoprotective effects by enhancing the antioxidant status, decreasing serum hepatic enzyme activities, and improving the lipid metabolism. This study suggested that the polysaccharides extracted and purified fromcould be exploited as a potent dietary supplement to attenuate aging and prevent age-related diseases.

BACKGROUND:The aim of the present study was to determine the therapeutic effects of medical ozone therapy on acute acetaminophen (APAP)-induced hepatotoxicity which were not clearly demonstrated in prior studies.

METHOD:Twenty-four mice were randomly assigned into three equal groups: Group 1 (control), Group 2 (APAP) and Group 3 (APAP +ozone). Hepatotoxicity was induced by APAP given as a single dose of 300 mg/kg intraperitoneally in Groups 2 and 3. Additionally, Group 3 received 20 mcg/0.5 mL ozone intraperitoneal twice a day for the remaining of the study. Other groups received saline injections. On the fourth day of the study, biochemical variables (AST, ALT, ALP) and liver histopathology wasassessed.

RESULTS:Intraperitoneal administration of a single dose of APAP induced hepatocellular damage that was shown by both liver enzymes and histopathological changes (p < 0.001). AST, ALT, ALP levels were elevated in both groups 2 and 3 and the difference from group 1 was statistically significant (p < 0.01).Mean ALT and AST levels of group 2 were statistically significantly higher versus group 3 (p < 0.01). In histopathological examinations; necrosis and inflammation were more prominent in Group 2 compared to Group 3 (p < 0.01).

CONCLUSION:Ozone showed beneficial effects on APAP hepatotoxicity at a statistically significant level. It is known that ozone has therapeutic effects in various diseases owing to its antioxidant effects. The present study suggests that ozone may be utilized as a routine supplementary therapy in acute APAP hepatotoxicity.

BACKGROUND:Dietary habit can play a key role in the prevention and treatment of fatty liver disease (NAFLD). Although many studies have investigated the effect of Mediterranean diet on NAFLD, findings are inconsistent and there is no systematic review on this topic. Therefore, the aim of this systematic review is to summarize the effect of Mediterranean diet on serum metabolic indices and anthropometric measures among NAFLD patients.

METHODS:We searched titles, abstracts, and keywords of articles indexed in Science Direct, MEDLINE, and Google Scholar databases up to October 2018 to identify eligible RCT studies. Randomized clinical trials assessing the effects of MD on NAFLD were included.

RESULTS:The present study included 10 randomized controlled trials, which involved a total of 856 adults with NAFLD. According to the result, MD may improve anthropometric measures, lipid profile, glycemic indices, liver enzyme, and NAFLD severity indices among patients with NAFLD.

CONCLUSION:We found that MD could alleviate NAFLD severity parameters but differences between studies should be taken into account. Finally, in order to draw a firm link between MD and NAFLD, more clinical trials with adequate sample size and better methodology should be done.

Extensive exercise induces inflammatory reactions together with high production of free radicals and subsequent liver and kidney tissues damage. This study was designed to investigate for effects of melatonin on liver and kidney tissues in the extensive exercise exposed rats and non-exercised rats. In this research, 24-male Sprague-Dawley rats were divided into four groups. For exercise rat model, the rats were exposed to slow pace running with the velocity of 10 m/min for 5 minutes for five days just before the study. And for last ten days after adaptation period, the exercise was improved as 15 min with the speed of 20 m/min and intra-peritoneal melatonin injection has been performed to the melatonin treated groups with the dose of 10 mg/kg. Biochemical results revealed a decrease in the parameters of kidney and liver enzymes in exercise-group and an increase in the parameters of serum, liver and kidney enzymes in the group that melatonin-exercise-group. As for histological analysis, while it is observed that there are cellular degenerations in the liver and kidney tissues with exercise application, a decrease has been observed in these degenerations in the group that melatonin was applied. At the end of the research, it has been determined that exercise application causes some damages on liver and kidney, and these damages were ameliorated with melatonin treatment.

BACKGROUND:We investigated whether vitamin C has protective effects on rat liver tissue treated with different dexmedetomidine doses.

MATERIAL AND METHODS:Thirty five wistar albino rats were randomly divided into 5 groups (Control (0.9 % NaCl intraperitoneally (ip), Dexmedetomidine 5μg.kg-1 (ip), Dexmedetomidine 5 μg.kg-1 ip plus Vitamin C (100 mg.kg-1), Dexmedetomidine 10 μg.kg-1 ip and Dexmedetomidine 10 μg.kg-1 ip plus Vitamin C (100 mg.kg-1). Histopathological liver injury, superoxide dismutase (SOD) activity and tissue Malondialdehyde levels were investigated.

RESULTS:Hepatocyte degeneration was significantly higher in D10 group than those in other study groups (p<0.0001, p = 0.002, p<0.0001, p = 0.005, respectively). Similarly, liver tissue sinusoidal dilatation and hepatocyte necrosis were significantly higher in D10 group than those in other groups (p<0.0001, p<0.0001, p = 0.002, p<0.0001 and p<0.0001, p = 0.046, p<0.0001 and p = 0.002, respectively). Tissue MDA levels in D10 group were significantly higher than those in control, D5+Vit C and D10+Vit C groups (p = 0.028, p = 0.004, p = 0.031, respectively). SOD enzyme activity in D10 group was significantly lower than in control, D5+Vit C and D10+Vit C groups (p<0.0001, p = 0.023 and p = 0.031, respectively).

CONCLUSION:High dose dexmedetomidine can induce hepatic injury and oxidative stress in rats while pre-treatment with vitamin C may be effective in protecting liver tissue against this newly recognized undesirable dexmedetomidine effect (Tab. 2, Fig. 5, Ref. 30).

Like several other anticancer drugs, methotrexate (MTX) causes side effects, such as neuropathic pain, hepatotoxicity, and nephrotoxicity. Abnormal production of reactive oxygen species has been suspected in the pathophysiology of MTX-induced hepatorenal toxicity. Therefore, the aim of this study was to investigate the probable protective role of vitamin C (Vit C) on oxidative stress induced by MTX in the liver and kidney tissues of rats. A total of 32 rats were randomly and equally divided into four groups. The first group served as the control group. The second group received a single dose of 20 mg/kg of MTX intraperitoneally. To demonstrate our hypothesis, the third and the fourth groups received 250 mg/kg of Vit C for 3 days by oral gavage, with or without MTX treatment. At the end of the study, the liver and kidney tissues of the rats were collected and examined using histology. Boththe tissues were assayed for malondialdehyde concentration and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities. In hepatic and renal tissues, lipid peroxidation levels were increased, whereas SOD, CAT, and GSH-Px levels were decreased by MTX. All parameters, including CAT levels in hepatic tissue, were significantly restored after the administration of Vit C for 3 days. Similar to the biochemical findings, evidence of oxidative damage was examined in both types of tissues by histopathological examination. From the results of this study, we were able to observe that Vit C administration modulates the antioxidant redox system and reduces the renal and hepatic oxidative stress induced by MTX. Vit C can ameliorate the toxic effect of MTX in liver and kidney tissues of rat.

Wolf (PCW) is an edible, pharmaceutical mushroom with remarkable biological properties including anti-tumor, anti-inflammation, anti-oxidation, anti-ageing, and anti-diabetic effects. In the current study, we investigated the effects of PCW extract on hepatic steatosis under in vitro and in vivo conditions, and elucidated the underlying mechanisms. In this study, a mixture of HepG2 cells treated with free fatty acid (FFA)-palmitic and oleic acid-and high-fat diet (HFD)-fed obese mice were used; in this background, the triglyceride (TG) levels in HepG2 cells and mice liver were measured, and the expression levels of genes associated with lipogenesis, fatty acid oxidation, endoplasmic reticulum (ER) stress, and autophagy were determined. Treatment of HepG2 cells with FFA enhanced intracellular TG levels in HepG2 cells, but co-treatment with PCW significantly attenuated the TG levels. Notably, PCW significantly enhanced the phosphorylation of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and sterol regulatory element-binding protein-1c (SREBP-1c) in FFA-treated HepG2 cells. PCW downregulated the expression of lipogenesis-related genes, but upregulated the expression of genes associated with fatty acid oxidation. Further, PCW inhibited FFA-induced expression of ER stress markers and induced autophagy proteins. However, inhibition of AMPK significantly attenuated the beneficial effects of PCW in HepG2 cells. Moreover, PCW efficiently decreased HFD-induced hepatic TG accumulation in vivo and increased the phosphorylation of hepatic AMPK. Three compounds present in PCW including poricoic acid, pachymic acid, and ergosterol, significantly decreased FFA-induced increase in intracellular TG levels, consistent with increased AMPK phosphorylation, suggesting that poricoic acid, pachymic acid, and ergosterol are responsible for PCW-mediated amelioration of hepatic steatosis. Taken together, these results demonstrated that PCW ameliorates hepatic steatosis through the regulation of lipid metabolism, inhibition of ER stress, and activation of autophagy in an AMPK-dependent manner. This suggested that PCW can be potentially used for the treatment of hepatic steatosis.