Carnitine Chloride Reduces the Severity of Experimental Hyperhomocysteinemia and Promotes Lactate Utilization by the Mitochondrial Fraction of the Rat Epididymis

Abstract

Hyperhomocysteinemia is a risk factor for many diseases, including reproductive disorders in men. L-carnitine is used in medical practice to correct impaired bioenergetic conditions; in patients with idiopathic forms of infertility its effects are associated with improvement of the sperm parameters. However, the effect of exogenous L-carnitine on the level of homocysteine in the gonadal tissues, as a risk factor for impaired fertility, has not been investigated yet. The aim of this study was to investigate activity of bioenergetic enzymes in the epididymal mitochondrial fraction, the dynamics of changes in the cytoplasmic and mitochondrial lactate levels and LDH activity, the total carnitine content, as well as the oxidative status of these cells under conditions of oxidative stress caused by hyperhomocysteinemia, and to assess the effect of carnitine chloride on these parameters under conditions of methionine administration to male Wistar rats. Methionine administration to animals for three weeks at a dose of 3 g/kg, resulted in development of the severe form of hyperhomocysteinemia with serum homocysteine concentrations exceeding 100 μmol/L. This was accompanied by a decrease in the activity of enzymes involved in the bioenergetic processes of the cell: tissue respiration (succinate dehydrogenase) and oxidative phosphorylation (H⁺-ATPase) in the epididymal head and tail. The change in lactate metabolism included an increase in its level in both the mitochondrial and cytoplasmic fractions of the epididymal head and mitochondria of the epididymal tail, and also simultaneous statistically significant decrease in LDH activity in the mitochondria and cytoplasm of the epididymal head. In male rats with severe hyperhomocysteinemia, an increase in the activity of mitochondrial SOD accompanied by an increase in the carbonylation of mitochondrial proteins in the head and tail of the epididymis was noted. Modeling of hyperhomocysteinemia under conditions of carnitine chloride administration led to different reactions of the cells of the studied tissues assayed in the epididymal head and tail homogenate. In the epididymal head, carnitine chloride promoted an increase in the mitochondrial lactate concentration and a decrease in the cytoplasmic lactate concentration, as well as an increase in the LDH activity associated with the mitochondrial fraction. These changes were accompanied by an increase in the activity of H⁺-ATPase in the epididymal, thus suggesting that carnitine chloride stimulated lactate transport into the mitochondria and its use as an energy substrate under conditions of oxidative stress caused by hyperhomocysteinemia. In the tail tissues, the changes were protective in nature and were associated with a decrease in the formation of oxidatively modified proteins.