Melatonin reduces toxicity induced by HAART in mice and HIV patients
JB Borges, FR Nerone, GF Messias, ALF Martins, M Spack Jr, ART Pupulin
Aims: Highly Active Antiretroviral Therapy (HAART) is the current care standard for treating patients with HIV/AIDS. Although HAART has is the only regimen potent enough to decrease viral load, adverse events may limit its efficacy. HAART-associated major toxic effects: neuropathy, myopathy, pancreatitis, hepatic steatosis, lactic acidosis and lipoatrophy, metabolic complications (insulin resistance and hyperlipidemia).Melatonin (N-acetyl-5-methoxytryptamine), the neuro-hormone synthetized during the night, has seen an unexpected extension of its functional implications toward type 2 diabetes development, sleep disturbances and depression. Melatonin has been shown to reduce the toxicity and increase the efficacy of a large number of drugs. Objective: This study evaluated the effects of melatonin supplementation (6mg / day / 30 days) in mice treated with antiretroviral therapy and AIDS patients using antiretroviral therapy (HAART). Material and Methods: For animal experiments mice were divided into experimental groups with 12 animals each: (I) animals treated with antiretroviral therapy for 15 days, (II) animals untreated animals treated with antiretroviral therapy and melatonin 6 mg/kg/day for 15 days, (III) untreated animals. Body weight, water intake and ration, excretion products and behavior were clinically assessed before and after treatment; further, serum cholesterol, triglycerides, hepatic enzymes (AST, ALT, GGT), creatinine, were evaluated by specific methods. For patient evaluation the study was carried out in a double-blind, placebo-controlled and completely randomized design. AIDS patients who had metabolic alterations were selected. Patients were divided into two groups: Group I (HAART) consisted of patients receiving placebo once a day in the evening. Group II (HAART+ Melatonin) comprised patients who received the melatonin (6 mg) once a day in the evening for one month. Clinical, emotional and laboratorial evaluation was performed before and after 30 days. Clinical evaluation was performed to assess the patients´ overall clinical state. Patients were instructed to report any complications. Laboratorial evaluation was performed. Glucose levels were determined by glucose oxidase method and ELISA (Genway Biotechnology, USA), respectively, following manufacturer’s instructions. Plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) were performed by the kinetic colorimetric method; triglycerides, total cholesterol and creatinine were performed by enzymatic colorimetric method, both provided by Gold Analisa Diagnóstica Ltda. Results: Animals treated with antiretroviral therapy and melatonin (II) had higher body weight gain, less hepatomegaly, less anxiety, lower levels of triglycerides, cholesterol and hepatic enzymes when compared to animals treated with antiretroviral therapy.Current study revealed that 40% (12/30) of the patients had changes in AST liver enzymes (> 38 U/I), 30% (9/30) had changes in ALT levels (> 38 U/I) and 30% (9/30) had GGT levels (> 40 U/I). Results obtained after the use of melatonin suggest melatonin activity on the liver. Significant differences between groups in plasma cholesterol indicate that melatonin exerted better improvement of blood lipid composition. Melatonin would lower cholesterol in liver and decrease plasma cholesterol. Above all, melatonin could decrease oxidative stress and improve dyslipidemia. Conclusion: Considering the low toxicity of melatonin and its ability to reduce the side effects and increase the efficacy of the drugs, its use may be important and significant as a combination therapy with HAART. Current study which investigated the effect of melatonin associated with antiretroviral treatment demonstrated that melatonin reduces toxicity induced by HAART. Melatonin improves metabolic abnormalities and emotional disturbs in animals and patients.
JB Borges, FR Nerone, GF Messias, ALF Martins, M Spack Jr, ART Pupulin. Melatonin reduces toxicity induced by HAART in mice and HIV patients. International Journal of Pharmacology and Clinical Research, Volume 1, Issue 1, 2019, Pages 12-24