Therapeutic efficacy of S-adenosylmethionine in chronic uranium intoxication in rats

Abstract

Introduction. Chronic exposure to uranium compounds causes adverse cytotoxic and immunopathological effects in the body.   The aim of the work was to evaluate the therapeutic efficacy of S-adenosylmethionine when administered intragastrically with respect to hepato-, nephro- and immunotoxic effects in chronic intoxicationwith uranyl acetate dihydrate (UAD).   Materials and methods. Chronic intoxication was modeled by injecting 85 male rats with UAD solution (5.0 mg/kg/day by element) for one month. S-adenosylmethionine was administered to animals at a dose of 72.7 mg/kg for 21 days.   Results. In chronic poisoning with UAD, 65% lethality, decrease of liver mass ratios (MR) and increase of renal MR were observed. Decrease in alkaline phosphatase activity, glucose level, lactic acid, number of CD4+ T-lymphocytes, increase in lactate dehydrogenase activity and creatinine level, number of CD8+ T-lymphocytes and apoptotic cell death, formation of catabolic pool of low and medium molecular weight substances (LMSMS) of blood plasma were registered. The results of urine analysis revealed the development of hyposthenuria, signs of glucosuria, hematosuria, proteinuria and leukocyturia, appearance of bilirubin in the urine. S-adenosylmethionine contributed to the decrease in the degree of target organ damage (reduction of fibroplastic and dystrophic changes in the liver and kidneys), normalization of immune system parameters (increase in CD4+ T-cells, decrease in CD8+ T-cells and frequency of apoptotic death of lymphocytes in immunocompromised animals) and endotoxicosis (decrease in the level of LMSMS from the catabolic pool area).   Discussion. According to the totality of all revealed pathological changes, UAD poisoning led to the development of tubulointerstitial nephritis, metabolic disorders of detoxification functions of the liver. The causes of animal death during the first week of the experiment were acute kidney damage or confluent pneumonia. The appearance of bilirubin in the urine was associated with porphyrin metabolism disorders. In the remote period of intoxication an imbalance of the T-cell link of the immune system developed, as well as, probably, a decrease in nonspecific resistance, which led to the development of pneumonia in rats.   Conclusion. S-adenosylmethionine therapy of hepato-, nephro- and immunotoxic effects in chronic UAD intoxication contributed to a decrease in the degree of damage to target organs, normalization of immune system parameters and endogenous intoxication.