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TO THE MECHANISM OF SEASONAL VARIATIONS IN CARBON TETRACHLORIDE TOXICITY


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Abstract

Introduction. Seasonal biorhythms can modify the toxic effect of xenobiotics. Natural fluctuations in hormone levels in the blood which can modify the metabolic processes in the liver can be the base of one of the mechanisms in this phenomenon. The study of the effector role of testosterone in seasonal chrono-reactivity can reveal one new link in the pathogenesis and will improve health risk assessment, especially in patients taking hormone therapy. The aim of the study was to reveal the role of testosterone in the mechanisms of chrono-reactivity the toxic effect for carbon tetrachloride in warm-blooded animals. Material and Methods. Studies were conducted on adult male Wistar rats, divided into negative control groups, a model with CCl4-induced toxic hepatitis, and experimental in which CCl4 exposure was carried out following a preliminary 7-day course of testosterone administration. Direct and total bilirubin, cholesterol, alkaline phosphatase, AlAT and AsAT, hydroperoxide and malondialdehyde were determined by standard methods. The experiment was repeated twice: both in winter and spring. Results. The amplitude of the damage to the structures and functions of hepatocytes from a single injection of the same poison dosage in winter and spring manifested in varying degrees, revealing the modulatory role of biological rhythms. Under premedication with testosterone, a similar tendency was observed in both series of the experiment (winter, spring): the toxic effect of CCl4 increased. This was recorded by the following biochemical changes: bilirubin increased by 55%, cholesterol - 19%, alkaline phosphatase - 12%, AlAT - 17%, AsAT - 35%, hydroperoxide - 29%, and malonic dialdehyde slightly (relative to groups with model toxic hepatitis). Conclusion. The male sex hormone regulating the metabolic activation of cytochromes in hepatocytes performing biotransformation is one of the effector links in the seasonal chrono-reactivity phenomena. The discovery of the whole mechanism will allow developing an effective system of chronoprophylaxis and reducing the risks of toxic poisoning in individuals during periods of maximum chrono-reactivity.


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