Evaluation of the regulatory effect of carnosine and alpha-lipoic acid on the cytokine profile of the cerebral cortex of Wistar rats under induced obesity

BACKGROUND: The model of obesity under experimental conditions is reproduced by using high-calorie diets in animals. It has been established that metabolic disorders cause meta-inflammation not only in peripheral organs and tissues, but also in brain structures. The search for effective neuroprotective antioxidants to suppress inflammatory processes in the cerebral cortex in obesity is an urgent task due to the widespread prevalence of this disease.

AIM: to evaluate the effect of minor biologically active substances — carnosine (CAR) and α-lipoic acid (ALA) on the cytokine profile of the frontal cortex of the left hemisphere of the brain in Wistar male rats with obesity induced by a high-calorie choline-deficient diet.

MATERIALS AND METHODS: The studies were carried out on male Wistar rats with an initial body weight of 150±10 g. The animals were randomized by body weight into 5 groups. For 8 weeks, rats of the 1st (control) group received a complete modified diet of AIN93M; rats of the 2nd group consumed a high-calorie choline-deficient diet (HCHDR), the fat content of which was 45%, fructose — 20% of the energy value of the diet; rats of the 3rd group received HCHDR with the addition of CAR at a dose of 75 mg per 1 kg of body weight; rats of the 4th group received HCHDR with the addition of ALA at a dose of 75 mg per 1 kg of body weight; rats of the 5th group received HCHDR with the addition of the CAR + ALA complex in a total dose of 150 mg per 1 kg of body weight. Animals were removed from the experiment by decapitation under ether anesthesia. The levels of triglycerides (Tg) and free fatty acids (FFA) in blood plasma (mmol) were determined on a biochemical analyzer (Konelab 20i, Thermo Clinical Labsystems Oy, Finland). Content of cytokines and chemokines (pg/ml): GM-CSF, IL-10, IL-17A, IL-12p40, IL-12p70, IL-1α, IL-2, IL-4, IL-5, IFN-γ, MCP-1, M-CSF, MIP-1α, MIP-2, MIP-3α, RANTES, and TNF-α in cerebral cortex lysates were determined by multiplex immunoassay using a Luminex 200 analyzer (Luminex Corporation, USA). To assess the relationship between the level of cytokines in blood plasma and changes in their concentrations under the influence of HCCDR in lysates of the cortex of the frontal lobe of the left hemisphere of the brain, the ratio was calculated: the level of cytokines pg/ml in blood plasma [1]/the content of cytokines pg/ml in lysates (pl/ lys) for each sample.

RESULTS: On the model of obesity in rats, the presence of an inflammatory process in the cerebral cortex was established, as evidenced by an increase in the content of pro-inflammatory factors: IL-2, M-CSF, MIP-1α and RANTES and a decrease in the content of immunoregulatory cytokines of varying severity: IL-10, IL17A, IL-12p40, IL-12p70, TNF-a, MIP-2 and MIP-3α in group 2 rats. (HCHDR) compared with the control group. Enrichment of HCHDR with biologically active substances: CAR, ALA or their complex, ensured the normalization of lipid metabolism, as evidenced by the decrease in the ratio of circulating Tg to FFA in the blood serum of rats to control values: 1st gr. (control) — 1,04±0.23; 2nd gr. (HCHDR) — 1,64±0.63; 3rd gr. (CAR) — 0,98±0.31; 4th gr. (ALA) — 0,86±0.31; 5th gr. (CAR+ALA) — 1,02±0.38. Enrichment of HCHDR with CAR, ALA or their complex led to a decrease in the content of pro-inflammatory and apoptosis-regulating cytokines and chemokines in the cortex of the frontal lobe of the rat brain: IL-1α, IL-2, IL-17A, M-CSF, MCP-1, MIP3α and RANTES, along with an increase in the level of the anti-inflammatory cytokine IL-10, which indicates the suppression of the inflammatory process induced by the consumption of HCHDR in rats.

CONCLUSION: The data obtained indicate the prospect of using CAR and ALA or their complex as neuroprotective antioxidants to reduce the inflammatory process in brain structures in obesity.

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