The ameliorating effect of Rutin on hepatotoxicity and inflammation induced by the daily administration of vortioxetine in rats.

BACKGROUND: Vortioxetine (VORTX) is a potent and selective type of selective serotonin reuptake inhibitor (SSRI) that is mainly prescribed for treating major depression along with mood disorders as the first drug of choice. Limited previous findings have indicated evidence of liver injury and hepatotoxicity associated with daily VORTX treatment. Rutin (RUT), which is known for its antioxidant properties, has demonstrated several beneficial health actions, including hepatoprotection. Therefore the current study aimed to evaluate and assess the ameliorative effect of RUT against the hepatotoxic actions of daily low and high-dose VORTX administration. METHODS: The experimental design included six groups of rats, each divided equally. Control, rats exposed to RUT (25 mg/kg), rats exposed to VORTX (28 mg/kg), rats exposed to VORTX (28 mg/kg) + RUT (25 mg/kg), rats exposed to VORTX (80 mg/kg), and rats exposed to VORTX (80 mg/kg) + RUT (25 mg/kg). After 30 days from the daily exposure period, assessments were conducted for serum liver enzyme activities, hepatotoxicity biomarkers, liver antioxidant endogenous enzymes, DNA fragmentation, and histopathological studies of liver tissue. RESULTS: Interestingly, the risk of liver damage and hepatotoxicity related to VORTX was attenuated by the daily co-administration of RUT. Significant improvements were observed among all detected liver functions, oxidative stress, and inflammatory biomarkers including aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), albumin, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), glutathione S-transferase (GST), total protein, acid phosphatase, N-Acetyl-/ß-glucosaminidase (ß-NAG), ß-Galactosidase (ß-Gal), alpha-fetoprotein (AFP), caspase 3, and cytochrom-C along with histopathological studies, compared to the control and sole RUT group. CONCLUSION: Thus, RUT can be considered a potential and effective complementary therapy in preventing hepatotoxicity and liver injury induced by the daily or prolonged administration of VORTX.

Ameliorative effect of hesperidin against high dose sildenafil-induced liver and testicular oxidative stress and altered gene expression in male rats.

BACKGROUND: The clinical use of sildenafil citrate (Viagra), a drug used to treat erectile dysfunction, is limited because of its many side effects on tissues. In this context, we aimed to investigate the protective effects of hesperidin, a citrus flavonoid, on hepatic and testicular damage induced by a high dose of sildenafil citrate in male rats. Rats were randomly divided into four groups. The first group was used as the control group. The second group was orally administered sildenafil citrate at a high dose of 75 mg/kg thrice a week. In the third group, hesperidin was administered orally at a dose of 50 mg/kg/day. The fourth group was administered 75 mg/kg sildenafil citrate three times a week with 50 mg/kg hesperidin daily. The experiment lasted for 28 days. RESULTS: In the sildenafil-treated groups, blood indices were altered, liver function tests were deranged, and serum testosterone levels were reduced. In the liver and testicular tissue, sildenafil citrate treatment resulted in significant reductions in catalase and total antioxidant capacity; as well as increased malondialdehyde, reactive oxygen species, and nitrous oxide levels. In addition, sildenafil citrate treatment caused abnormal histopathological patterns in both the liver and the testes. Liver vascular endothelial growth factor and testicular steroidogenic acute regulatory protein gene expression were upregulated. CONCLUSIONS: Hesperidin attenuated the harmful effects of intensive sildenafil citrate treatment on liver and testicular functions, alleviated oxidative stress and normalized blood indices. Therefore, hesperidin could be protective against sildenafil citrate-induced oxidative damage that may develop over the long term.

Protective and restorative potency of diosmin natural flavonoid compound against tramadol-induced testicular damage and infertility in male rats.

Flavonoids are polyphenolic natural compounds with various biological actions and limited toxicity including diosmin (DM) which is considered a safe flavonoid natural type with anti-inflammatory and antioxidant activities. Tramadol (TM) is a centrally long-acting analgesic class of opioids extensively being used among the population. It was reported that long-term exposure to TM triggers the releases of oxidative stress, inflammatory factors, and nitric oxides resulting in organs damage. This study aimed to investigate the possible ameliorative and restorative actions of DM against tramadol-induced testicular damage. Rats were divided into: GI: control; GII: Rats received TM, GIII: Rats received DM, GIV: Rats received TM + DM; GV: Rats received DM + TM. Rat's testicular tissue and blood samples were collected. A relevant improvement in all examined parameters was observed among GIV and GV groups. Thereby, it was highlighted that diosmin has beneficial natural actions against tramadol-induced testicular injury via suppressing triggered oxidative stress, and inflammatory factors.

Mitigative effect of caffeine against diclofenac-induced hepato-renal damage and chromosomal aberrations in male albino rats.

BACKGROUND: Among the most commonly consumed non-steroidal anti-inflammatory drugs (NSAID) is Diclofenac (Dic), especially in low-income countries due to its high efficiency and affordable price. However, the continuous administration of Diclofenac may induce toxic effects on various body organs including the liver and kidney. Caffeine (Caf) (1,3,7-trimethylxanthine) is a pharmacologically active alkaloid type with antioxidant and anti-inflammatory actions. AIM: The current study aims to evaluate the ameliorative effect of Caffeine against Dic-induced hepato-renal toxicity and damage. METHODS: Twenty-four male albino rats type were assigned randomly into four groups (n = 6): (Group 1): Control group, (Group 2): Six male rats were exposed to Dic 10 mg/kg intraperitoneally (I.P) for 28 days, (Group 3): Six male rats were exposed to Caf (15 mg/kg orally) for 28 days; (Groups 4): Six male rats were exposed to Dic (10 mg/kg, i.p) + Caf (15 mg/kg, orally) for 28 days. Histopathological study and various biological parameters were estimated among the four groups including hemoglobin (Hb%) red blood cells (RBCs), Hematocrit (HT%), total leucocyte count (WBCs), lipid peroxidation (LPO), glutathione peroxidase (GPx), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine, tumor necrosis factor-α (TNF-α), and nitric oxide (NO). RESULTS: The administration of Diclofenac resulted in significant deteriorations in the histopathological findings and estimated biological parameters. Whereas, daily Caffeine administration ameliorated Diclofenac-induced toxicity in the kidney and liver by three mechanisms including antioxidant, anti-inflammatory, and DNA damage inhibition. CONCLUSION: The current study demonstrated the promising ameliorative and protective effects of Caffeine against Diclofenac-induced hepatic and renal injury.