Preconditioning with atorvastatin against renal ischemia-reperfusion injury in nondiabetic versus diabetic rats.

Acute renal failure complicates renal ischemia-reperfusion (I/R) owing to reactive oxygen species production. Atorvastatin (ATO) has anti-inflammatory and antioxidant properties. The current study investigated whether ATO alleviated damage induced by renal I/R injury in nondiabetic versus diabetic rat models. Thirty-six rats were equally divided into 6 groups: group A1 (nondiabetic sham), group A2 (nondiabetic I/R), group A3 (nondiabetic ATO + I/R), group B1 (diabetic sham), group B2 (diabetic I/R), and group B3 (diabetic ATO + I/R). All groups experienced 45 min of bilateral renal ischemia followed by 24 h of reperfusion. Groups A3 and B3 were treated with single intraperitoneal doses of ATO (10 mg/kg) 30 min before ischemia. Histological analysis of kidney tissues, kidney function tests, and analyses of caspase-3 and CD44 expression and oxidative stress markers were performed to assess tubular injury. Histological analysis revealed marked tubular damage in groups A2 and B2 but improvement in groups A3 and B3. Improvements were also found in groups A3 and B3 for caspase-3 and CD44 expression, kidney function tests, and oxidative stress markers. Our results suggest ATO may ameliorate renal I/R injury differently between nondiabetic and diabetic rats.

Histological, immunohistochemical, and molecular investigation on the hepatotoxic effect of potassium dichromate and the ameliorating role of Persea americana mill pulp extract.

The current study has been designed to assess the role of Persea americana (P. americana) pulp extract on potassium dichromate-induced hepatotoxicity in rats. P. americana pulp extract administration improved the hepatic vascular congestion, blood extravasation, inflammatory cellular infiltration, Kupffer cell hyperplasia, and nuclear changes. It also significantly ameliorated hepatic interstitial and peri-portal fibrosis and caused retrieval of the PAS-positive reaction in the liver parenchyma and around the central vein with restoration of the glycogen granules. P. americana also significantly attenuated the immunohistochemical expression of NF-kß p65 and its downstream inflammatory cytokines IL6 and TNFα in the liver parenchyma. The antioxidant effect of P. americana was evidenced by significant modulation of the three major components of the thioredoxin (Trx) antioxidant system, the Trx, the thioredoxin reductase (TrxR), and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase along with significant increase in the level of superoxide dismutase and glutathione, and decrease in the lipid peroxidation product malondialdehyde. P. americana pulp extract also caused significant elevation of hepatic protein phosphatase 5 with subsequent down-regulation of Apoptosis signal-regulating kinase1 (ASK1) and its downstream signaling targets MAPK kinase 4 (MKK4), p38 mitogen-activated protein kinases (p38-MAPKs), the c-JUN N-terminal kinase (JNK), and the extracellular signal-regulated kinase 1/2 (ERK 1/2). Also, In conclusion, P. americana pulp extract has anti-oxidative and anti-inflammatory effects against potassium dichromate-induced hepatotoxicity.