To investigate mechanisms by which thymoquinone (TQ) can prevent methotrexate- (MTX-) induced hepatorenal toxicity, TQ (10 mg/kg) was administered orally for 10 days. In independent rat groups, MTX hepatorenal toxicity was induced via 20 mg/kg i.p. at the end of day 3 of experiment, with or without TQ. MTX caused deterioration in kidney and liver function, namely, blood urea nitrogen, creatinine, alanine aminotransferase, and aspartate aminotransferase. MTX also caused distortion in renal and hepatic histology, with significant oxidative stress, manifested by decrease in reduced glutathione and catalase, as well as increase in malondialdehyde levels. In addition, MTX caused nitrosative stress manifested by increased nitric oxide, with upregulation of inducible nitric oxide synthase. Furthermore, MTX caused hepatorenal inflammatory effects as shown by increased tumor necrosis factor-α, besides upregulation of necrosis factor-κB and cyclooxygenase-2 expressions. MTX also caused apoptotic effect, as it upregulated caspase 3 in liver and kidney. Using TQ concurrently with MTX restored kidney and liver functions, as well as their normal histology. TQ also reversed oxidative and nitrosative stress, as well as inflammatory and apoptotic signs caused by MTX alone. Thus, TQ may be beneficial adjuvant that confers hepatorenal protection to MTX toxicity via antioxidant, antinitrosative, anti-inflammatory, and antiapoptotic mechanisms.

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Background:Intestinal toxicity is a serious side effect in methotrexate (MTX) chemotherapy.Objective:To investigate the mechanisms by which the anticancer drug MTX-induced intestinal damage could be prevented by thymoquinone (TQ), an active ingredient of Nigella sativa.Materials and Methods:TQ was given orally for 10 days, and MTX toxicity was induced at the end of day 3 of the experiment, with or without TQ pretreatment.Results:MTX caused intestinal damage, represented by distortion in normal intestinal histological structure, with significant oxidative stress, exhibited as decrease in reduced glutathione concentration and catalase activity, along with significant increase in malondialdehyde level compared to control group. MTX also caused nitrosative stress evident by increased intestinal nitric oxide (NO) level, with up-regulation of inducible NO synthase expression shown in immunohistochemical staining. Furthermore, MTX caused inflammatory effects as evident by up-regulation of intestinal necrosis factor-kappa beta and cyclooxygenase-2 expressions, which were confirmed by increased intestinal tumor necrosis factor-alpha level via enzyme-linked immunosorbent assay. Moreover, MTX caused apoptotic effect, as it up-regulated intestinal caspase 3 expression. Concomitant TQ significantly reversed the MTX-induced intestinal toxic effects by reversing intestinal microscopic damage, as well as significantly improving oxidative/nitrosative stress, inflammatory and apoptotic markers tested compared to MTX alone.Conclusion:TQ may possess beneficial intestinal protective effects as an adjuvant co-drug against MTX intestinal toxicity during cancer chemotherapy. TQ protection is conferred via antioxidant, anti-nitrosative, anti-inflammatory, and anti-apoptotic mechanisms.SUMMARY Methotrexate induces oxidative and nitrosative stress in intestinal tissuesMethotrexate also initiates inflammatory and apoptotic intestinal injuryThymoquinone co-administration ameliorates methotrexate-induced intestinal toxicityThymoquinone has antioxidative, anti-nitrosative, anti-inflammatory, and anti-apoptotic mechanisms. Abbreviations used: COX-2: Cyclooxygenase-2, ELISA: Enzyme-linked immunosorbent assay, H and E: Hematoxylin and eosin, iNOS: Inducible nitric oxide synthase, MDA: Malondialdehyde, MTX: Methotrexate, NO: Nitric oxide, NF-κB: Nuclear factor-κB, GSH: Reduced glutathione, TQ: Thymoquinone, TNF-α: Tumor necrosis factor-alpha

Background: Silver nanoparticles (AgNPs) are considered one of the most commonly used nanoparticles due to its broad antimicrobial activity. However, the toxic effects of nanoparticles on normal cells and living organs are still not fully determined. Objectives: the present study was designed to investigate the toxicity of silver nanoparticles on liver, kidneys, brain and spleen in mice and to explore the possible mechanisms behind it. Material and Methods: 16 male mice from local strain were randomly classified into (1) control group (2) silver nanoparticles treated group; mice were orally administered AgNPs (1mg/kg/day) for 28 days. Biochemical analysis for serum levels of liver transaminases, urea and creatinine, lipid peroxides, reduced glutathione, superoxide dismutase, total antioxidant capacity and TNF-α were done in addition to histopathological examination for the four organs. Results: silver nanoparticles treated group showed significantly elevated serum levels of liver transaminases, urea and creatinine together with significant high levels of lipid peroxides and TNF-α with significant decrease in serum levels of reduced glutathione, superoxide dismutase and total antioxidant capacity. Histopathology of the organs revealed tissue damages in AgNPs treated group evidenced by disturbed organ architecture, congestion, increased inflammatory cells with signs of necrosis. Conclusion: administration of silver nanoparticles produced remarkable toxic effects to the liver, kidneys, brain and spleen of mice, probably via activation of oxidative stress and inflammatory processes in these organs.

Background: Statins are the most effective and best tolerated agents for treating hyperlipidemia. They have many side effects. The most common side effect in statins users is myopathy.