ABSTRACT
Gentamicin (GNT)-induced nephrotoxicity culminates into renal failure with a possible cardiovascular impact. Garlic extract (GE) is a cardiovascular protectant with limited mechanistic data. Therefore, we assessed the disturbance in specific cardiac parameters and the potential protective effect of GE supplementation against them in a rat model of GNT-induced chronic renal failure (CRF). Adult male rats (n = 24) were randomly assigned into four groups (n = 6 each): normal controls (CON), garlic extract controls (GE; 250 mg kg-1, orally), GNT-induced CRF (GNT; 100 mg kg-1, i.p.), and GNT + GE (GNT and GE in the same previous doses) groups. GNT and GE were given daily for 3 weeks. Animals co-treated with GNT and GE exhibited improved renal functions, body weight (BW), and heart weight (HW)/BW ratio; declined blood pressure; lowered plasma levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and total peroxides (TP); and elevated total antioxidant capacity (TAC) levels. Moreover, the heart tissue contained raised levels of TAC and Na+/K+-ATPase activity and lowered levels of TP and Ca2+. Findings provide evidence that administration of GE in experimental CRF model helped protect the heart through reducing oxidative stress and controlling cardiac Na+/K+-ATPase activity and Ca2+ levels.
Subject(s)
Anti-Bacterial Agents/toxicity , Cardiotonic Agents/therapeutic use , Garlic , Gentamicins/toxicity , Kidney Failure, Chronic/drug therapy , Phytotherapy , Animals , Blood Pressure/drug effects , Body Weight/drug effects , Calcium/metabolism , Creatine Kinase, MB Form/blood , Creatinine/blood , Disease Models, Animal , Heart/drug effects , Kidney Failure, Chronic/chemically induced , Kidney Failure, Chronic/enzymology , Kidney Failure, Chronic/metabolism , L-Lactate Dehydrogenase/blood , Male , Myocardium/enzymology , Myocardium/metabolism , Myocardium/pathology , Organ Size/drug effects , Oxidative Stress/drug effects , Plant Extracts/therapeutic use , Rats, Wistar , Sodium-Potassium-Exchanging ATPase/metabolismABSTRACT
Little is known about the role of tumor necrosis factor-alpha (TNF-α), plasminogen activator inhibitor-1 (PAI-1), and inducible nitric oxide synthase (iNOS) in the gastric ulcer and the effect of alpha lipoic acid (ALA) in their modulation. Hence, this experimental study was designed to assess the possible protective effect of ALA against indomethacin (IND)-induced gastric ulcer in rats, as well as to determine the possible underlying mechanisms with a special focus on TNF-α, PAI-1, and iNOS. Adult male rats (nâ¯=â¯28) were divided into four equal groups: the control group received distilled water, the vehicle group received 0.5% carboxymethylcellulose, the ulcer group received a single oral dose of IND (50â¯mg/kg) and the ALA-treated group received ALA (100â¯mg/kg) orally for 3 days before ulcer induction. Four hours after IND administration, all rats were sacrificed. The ulcer index, and gastric tissue homogenate contents of total antioxidant capacity (TAC), malondialdehyde (MDA), TNF-α, and PAI-1 were evaluated. Immunohistochemical evaluation of iNOS protein expression and histopathological examination of gastric tissue were investigated. The results revealed that ALA pretreatment significantly decreased the ulcer index, the gastric levels of MDA, TNF-α, PAI-1, and iNOS protein expression while increased the gastric levels of TAC as well as improved the histopathological appearance of gastric tissues. In conclusion, ALA ameliorated the IND-induced gastric ulceration. This could be attributed to its antioxidant and anti-inflammatory activities via suppression of TNF-α-induced elevation of both PAI-1 level and iNOS expression in the gastric tissue.
