Effects of Cyclosporine Therapy on Liver and Kidney Retrieval in Poisoned Male Rats by Mesobuthus eupeus Scorpion Venom

Abstract

Background: Mesobuthus eupeus venom is a member of Buthidae family, which can enter the blood circulation exerting detrimental effects on body organs, such as the liver and kidney through inflammation. Cyclosporine, known as an anti-inflammatory drug, is used to treat many inflammation-associated diseases. Objectives: In this study, cyclosporine was selected to inhibit the scorpion toxin effects on rat organs. Methods: This experimental study was conducted in the Razi Vaccine and Serum Research Institute, Agricultural Research Education and Extension Organization, Karaj, Iran, from June to November 2019. Fifty male rats were randomly divided into five groups of 10, including the control (10 mg/kg olive oil i.p), M. eupeus venom (10 mg/kg i.p.), cyclosporine 10 mg/kg (venom 10 mg/kg for 30 min i.p followed by cyclosporine 10/kg mg for 7 day i.p.), cyclosporine 20 mg/kg (venom 10 mg/kg for 30 min i.p followed by cyclosporine 20 mg/kg for 7 day i.p.), and cyclosporine 30 mg/kg (venom 10 mg/kg for 30 min i.p followed by cyclosporine 30 mg/kg for 7 day i.p.). After treatment with cyclosporine, the liver and kidney function was analyzed by calculating some biochemical enzymes, including serum glutamate-pyruvate transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT), nitric oxide (NO), interleukin-2 (IL-2), malondialdehyde (MDA), creatinine, and urea via ELISA and spectrophotometry. Then, to determine the rate of apoptosis in tissue, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling method was done. Results: At the end of the study, the results showed a significant elevation in SGPT (164.5 ± 10 vs. 126.2 ± 7, P < 0.0001), SGOT (190.37 ± 11 vs. 148 ± 10, P < 0.0001), NO (24.4 ± 1.17 vs. 17.4 ± 1.4, P = 0.02), and MDA (0.42 ± 0.05 vs. 0.22 ± 0.04, P < 0.0001) in the venom group compared with the control group. There were no significant differences in the urea, IL-2, and creatinine between the venom and control groups. However, the group receiving cyclosporine (30 mg/kg) showed a significant decline in SGPT (96.42 ± 5.7 vs. 164.5 ± 10, P < 0.0001), SGOT (144.57 ± 9.24 vs. 190.37 ± 11, P < 0.0001), urea (28.83 ± 1.32 vs. 38.83 ± 1.6, P = 0.00), creatinine (0.023 ± 0.01vs. 0.29 ± 0.005, P < 0.0001), and MDA (0.10 ± 0.01 vs. 0.42 ± 0.05, P < 0.0001), as well as increased apoptosis rate (P < 0.05), compared with the venom group. No significant difference was observed between the cyclosporine and venom groups in NO and IL-2. Conclusions: Cyclosporine at a dose of 30 mg was able to decrease inflammatory responses and induce apoptosis rate. Therefore, it could be a suitable drug for patients bitten by a scorpion sting.