Diacerein mitigates adenine-induced chronic kidney disease in rats: Focus on TLR4/MYD88/TRAF6/NF-κB pathway.

Chronic kidney disease (CKD) is a serious problem which negatively affects human health. AIMS: The purpose of this investigation was to explore the possible beneficial impacts of diacerein on adenine-induced CKD in rats. MAIN METHODS: 32 male Sprague Dawley rats were allocated into 4 groups; normal, diseased (200 mg/kg adenine, orally) and diacerein (25 and 50 mg/kg, orally). KEY FINDINGS: Adenine produced marked reduction in rats' body weights and a substantial increase in kidney/body weight index. Additionally, adenine significantly increased serum creatinine and BUN levels besides proteinuria levels, and also reduced creatinine clearance. Adenine induced oxidative stress as evidenced by increased MDA content and diminished GSH concentration in renal tissues. These biochemical measurements were confirmed by the morphological and histopathological results. Moreover, adenine revealed substantial elevation in renal level and expression of MYD88, TRAF6 and TNF-α, and renal level of IL-1ß in addition to increased expression of TLR4, NF-κB p65 and p-NF-κB p65 while reduced the expression of IκB-α. Diacerein in a dose-dependent manner effectively ameliorated adenine-induced alterations. SIGNIFICANCE: Diacerein could be used as a therapeutic agent to attenuate CKD after further clinical studies.

Comparative neuroprotective effects of Cerebrolysin, dexamethasone, and ascorbic acid on sciatic nerve injury model: Behavioral and histopathological study.

Background: The majority of the suggested experimental modalities for peripheral nerve injury (PNI) result in varying degrees of recovery in animal models; however, there are not many reliable clinical pharmacological treatment models available. To alleviate PNI complications, research on approaches to accelerate peripheral nerve regeneration is encouraged. Cerebrolysin, dexamethasone, and ascorbic acid (vitamin C) drug models were selected in our study because of their reported curative effects of different mechanisms of action. Methodology: A total of 40 adult male albino rats were used in this study. Sciatic nerve crush injury was induced in 32 rats, which were divided equally into four groups (model, Cerebrolysin, dexamethasone, and vitamin C groups) and compared to the sham group (n = 8). The sciatic nerve sensory and motor function regeneration after crushing together with gastrocnemius muscle histopathological changes were evaluated by the sciatic function index, the hot plate test, gastrocnemius muscle mass ratio, and immune expression of S100 and apoptosis cascade (BAX, BCL2, and BAX/BCL2 ratio). Results: Significant improvement of the behavioral status and histopathological assessment scores occurred after the use of Cerebrolysin (as a neurotrophic factor), dexamethasone (as an anti-inflammatory), and vitamin C (as an antioxidant). Despite these seemingly concomitant, robust behavioral and pathological changes, vitamin C appeared to have the best results among the three main outcome measures. There was a positive correlation between motor and sensory improvement and also between behavioral and histopathological changes, boosting the effectiveness, and implication of the sciatic function index as a mirror for changes occurring on the tissue level. Conclusion: Vitamin C is a promising therapeutic in the treatment of PNI. The sciatic function index (SFI) test is a reliable accurate method for assessing sciatic nerve integrity after both partial disruption and regrowth.

Empagliflozin mitigates methotrexate-induced hepatotoxicity: Targeting ASK-1/JNK/Caspase-3 pathway.

Methotrexate (MTX) administration causes hepatotoxicity, a serious side effect limiting its clinical use. Therefore, this study was performed to investigate the beneficial effect of empagliflozin (Empa) against MTX-induced hepatotoxicity. Adult male albino mice were pre-treated with Empa (at 10 or 25 mg/kg/d, orally) for 6 days and then received a single MTX injection (at 20 mg/kg, intraperitoneally). Empa effectively ameliorated MTX-induced structural and functional alterations. It significantly decreased transaminase, alkaline phosphatase, and gamma-glutamyl transferase levels and increased albumin levels in the serum. Moreover, Empa restored the oxidant/antioxidant balance as indicated by reduced malondialdehyde and total nitrite/nitrate contents and elevated reduced glutathione level and superoxide dismutase activity. Additionally, Empa (10 and 25 mg/kg) markedly suppressed the elevated levels of tumor necrosis factor-alpha, interleukin-6, apoptosis signal-regulating kinase1, c-Jun N-terminal kinase, BCL2 associated X protein, and Caspase-3 in hepatic tissues and increased the hepatic interleukin-10 levels. Furthermore, Empa substantially decreased nuclear factor kappa B expression in hepatic tissues. These biochemical findings were further confirmed by histopathological and transmission electron microscopy observations. Therefore, Empa might be used as an adjuvant to ameliorate MTX-induced hepatotoxicity after further clinical evaluation.