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.

Liver fibrosis is a major health problem that can lead to the development of liver cirrhosis and hepatocellular carcinoma. On the other hand, several antioxidants have been shown to possess protective effect against liver fibrosis. Therefore, in the present work, the effectiveness of curcumin, α-lipoic acid, and N-acetylcysteine in protecting against carbon tetrachloride (CCl(4))-induced liver fibrosis as well as the mechanism(s) implicated in this protective effect was studied. The antioxidants used in this study resulted in hepatoprotective effect as evident by substantial decreases in collagen deposition in histopathological examinations in addition to significant decrease in serum levels of alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transpeptidase, bilirubin, and transforming growth factor-alpha (TGF-α) as well as hepatic malondialdehyde concentration, with a concurrent increase in serum matrix metalloproteinase-13 (MMP-13) and hepatic reduced glutathione (GSH) levels as compared to CCl(4) fibrotic group. In conclusion, curcumin, α-lipoic acid, and N-acetylcysteine protect rats against CCl(4)-induced liver fibrosis most possibly through their antioxidant activities and their capacities to induce MMP-13 and to inhibit TGF-α levels.

Staphylococcus aureus isolates are the major pathogens responsible for wound and surgical site infections at MUH and MRSA are a potential threat for wound patients in Egypt.

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