Cytoprotective effects of DL-alpha-lipoic acid or squalene on cyclophosphamide-induced oxidative injury: An experimental study on rat myocardium, testicles and urinary bladder

• Published in: Food and chemical toxicology Vol. 48; no. 8; pp. 2326 - 2336
• Main Authors: Motawi, Tarek M.K., Sadik, Nermin A.H., Refaat, Ayat
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.08.2010; Elsevier
• Subjects: Animals; Antineoplastic Agents, Alkylating - antagonists & inhibitors; Antineoplastic Agents, Alkylating - toxicity; Antioxidants - metabolism; Antioxidants - pharmacology; Biological and medical sciences; Biomarkers; Body Weight - drug effects; Calcium - metabolism; Cell Survival - drug effects; Cyclophosphamide; Cyclophosphamide - antagonists & inhibitors; Cyclophosphamide - toxicity; Heart; Lipoic acid; Male; Medical sciences; Myocardium - pathology; Nitric Oxide - metabolism; Oxidative Stress - drug effects; Rats; Rats, Wistar; Squalene; Squalene - pharmacology; Survival; Testes; Testis - pathology; Thioctic Acid - pharmacology; Toxicology; Urinary bladder; Urinary Bladder - pathology; Heart; NO; Lipoic acid; 3β-HSD; ALP; LPO; MDA; 17β-HSD; LDH; T; Urinary bladder; RNS; SDH; DHLA; iNOS; FRAP; Hb; GSH; SQ; GSSG; AST; γ-GT; Squalene; GR; CP; ACP; GPx; Cyclophosphamide; LA; ROS; TAC; HC; Testes; CPK; Antineoplastic agent; Rat; Toxicity; Rodentia; Experimental study; Testicle; Male genital system; Alkylating agent; Oxazaphosphinane derivatives; Vertebrata; Mammalia; Urinary system; Cytoprotector; Nitrogen mustard; Animal; Myocardium; Circulatory system
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2010.05.067

The present study aimed to evaluate the role of DL-alpha-lipoic acid (LA) and squalene (SQ) on oxidative cardiac, testicular and urotoxic damage induced by cyclophosphamide (CP). Male Wistar rats were divided into four groups; three groups received a single intraperitoneal injection of CP (200 mg/kg BW) to induce toxicity, and two of these groups received either LA (35 mg/kg BW) or SQ (0.4 ml/rat) orally 7 days before and 7 days after CP injection. A vehicle-treated control group was also included. Oxidative damage was observed by decreased serum total antioxidant capacity (TAC) level and abnormal alterations in glutathione peroxidase (GPx) and glutathione reductase (GR) activities, levels of glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO) and calcium (Ca +2) in the heart, testes and urinary bladder of CP-administered rats. Cardiac marker enzyme activities; creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and aspartate transaminase (AST) showed severe declines whereas testicular markers; sorbitol dehydrogenase (SDH), γ-glutamyl transferase (γ-GT), acid and alkaline phosphatases (ACP and ALP), serum testosterone (T) level and haemoglobin (Hb) absorbance were abnormal. Histopathological observations were also altered. These CP-induced pathological alterations were attenuated by treatment with LA or SQ. These findings highlight the efficacy of LA and SQ as cytoprotectants in CP-induced toxicity.