Potential antidotal effect of naloxone against captopril acute toxicity in albino rats

Captopril, is an angiotensin converting enzyme inhibitor which is widely used in the management of hypertension, has many new potential applications opening the way for wider deployment. Naloxone which is an opioid antagonist was reported to block the inhibitory effect of B-endorphin on the centrally mediated pressure action of angiotensin II thus reversing hypotension. This work aimed at evaluating the acute toxic effects of captopril and to detect the potential protective role of naloxone in ameliorating this toxicity. Seventy adult albino rats of both sexes were divided into 7 equal groups. Group [I]. [II] and [III: negative and positive control groups. Group [IV] [Naloxone group]: naloxone was given in a single I.P dose of 0.06mg/rat. Group [V] [Captopril group,: Captopril was given in a single toxic oral dose of 13.5mg/rat. Group [VI] [Captopril and Naloxone]: a single I.P dose of naloxone [0.06mg/rat] was given 1 hour after captopril single oral toxic dose. Group [VII]: A single I.P dose of naloxone [0.06mg/rat] was given 2 hours after captopril single oral toxic dose. After 24 hours from naloxone intake. the animals were anaesthesized, blood pressure and pulse rate were measured after aortic exposure. Then the animals were sacrificed and blood samples were collected for investigating liver function tests, kidney function tests and serum electrolytes. Liver and kidney specimens were also examined histologically. It was found that captopril significantly decreased the blood pressure but did not affect pulse rate. Captopril also significantly affected the liver function tests. kidney function tests, and serum electrolytes. The administration of naloxone 1 hour and 2 hours after captopril significantly improved blood pressure, liver function tests, kidney function tests and serum electrolytes There was non significant difference between the administration of naloxone 1 hour or 2 hours after captopril. The biochemical results were coinciding with the histological results. So, naloxone was found to have an antidotal effect against captopril toxicity. The very common use of captopril in medical practice, together with the severity of the toxicity, may cause calls for increased awareness and an antidotal management

Alpha-lipoic acid versus nimodipine protective effect against vinblastine induced neurological and haematological toxicities in adult albino rats

Vinblastine [VBL] is an antimicrotubule vinca alkaloid that is used for the treatment of resistant metastatic breast cancer. In this work, it had been studied in adult albino rats to define its neurological and haematological toxicities. Alpha lipoic acid and nimodipine were used to evaluate their protective role against VBL induced toxicities. 63 adult albino rats of both sexes were divided into 9 equal groups: negative control group [Gr I], olive oil group [Gr II], 5% dextrose solution group [Gr III], Alpha-lipoic acid group [Gr IV], nimodipine group [Gr V], VBL group [Gr VI], Alpha-lipoic acid + VBL group [Gr VII], nimodipine + VBL group [Gr VIII] and Alpha-slipoic acid + nimodipine + VBL group [Gr IX]. The materials and drugs were given intraperitoneally for 2 consecutive days every 3 weeks [1 cycle] and the course was repeated for six cycles. Neurological investigations were carried out by the flowcytometer and the spectrophotometer for detection of the percentage of both the apoptotic cells in the pre G1 phase and the DNA fragmentation. Haematological investigations included CBC s and bone marrow film examination. The chain breaking antioxidants were also measured. The results revealed that VBL had neurological and haematological toxicities while Alpha-lipoic acid and nimodipine showed protective effects against such toxicities. The protective effect of Alpha-lipoic acid was better than nimodipine as regards the haematological toxicity. The best protection was offered by combined administration of [Alpha-lipoic acid + nimodipine with VBL