Mechanisms of Thymoquinone Hepatorenal Protection in Methotrexate-Induced Toxicity in Rats

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

Urinary and tissue monocyte chemoattractant protein1 (MCP1) in lupus nephritis patients

Aim of the work: To assess the role of urinary and tissue monocyte chemoattractant protein-1 (MCP-1) in active lupus nephritis (LN) and to correlate the levels with disease activity and renal status. Patients and methods: Urinary and tissue MCP-1 were determined in 42 systemic lupus erythematosus (SLE) patients with LN. 20 matched controls were considered. SLE disease activity index (SLEDAI) was recorded in all patients. Urinary and renal tissue MCP-1 was evaluated. Renal biopsy was performed in active LN patients for histopathological classification and correlation. Results: 22 active LN patients (22.8 ± 4.7 years old) and 20 inactive (24.6 ± 4.3 years old) were studied. They were 39 female and 3 males (F:M 13:1). The urinary MCP-1 was significantly higher in active LN patients (1072.8 ± 658.4 pg/mg creatinine) compared to the inactive group (151.3 ± 103.5 pg/mg creatinine) and both were significantly higher than the level in the controls (19 ± 17.8 pg/mg creatinine) (p < 0.001). A significant correlation was present in the active LN patients between urinary MCP-1 level and proteinuria, anti-dsDNA, renal SLEDAI and biopsy activity index and negatively with C3 and C4. There was a significant correlation of the glomerular MCP-1 renal tissue expression score with the renal SLEDAI, anti-dsDNA, biopsy activity index and urinary MCP-1 and negatively with C3. Tubulointerstitial MCP-1 score significantly correlated with urinary MCP-1. Urinary, glomerular and tubular MCP-1 showed a sensitivity of 97%, 64% and 4% and specificity of 100%, 95% and 20% respectively in detecting LN. Conclusion: MCP-1 could be a valuable marker for LN and disease activity