The effect of non-steroidal anti-inflammatory drugs with different mechanisms of action on the body temperature and cyclooxygenase pathway of the arachidonic acid cascade on the model of acute general cooling (air hypothermia) in rats.

NSAIDs are promising agents for preventing cold injury (frigoprotectors). The influence of prophylactic administration of the non-selective COX inhibitor diclofenac sodium (7 mg/kg) and the highly selective COX-2 inhibitor etoricoxib (5 mg/kg) on cyclooxygenase pathway biomarkers was studied on the model of acute general cooling (air hypothermia at -18 °С for 2 hours). Diclofenac completely prevented a decrease in body temperature, surpassing etoricoxib. In the liver of the rats immediately after cold exposure, the content of COX-1 was increased moderately and the content of COX-2 highly significantly. Very significantly, the level of PGE2 decreased, and the levels of PGF2α, especially PGI2 and TXB2, were elevated. In the blood serum, the level of COX-1 was decreased, and the changes in COX-2 and prostaglandins levels were similar to those in the liver. Diclofenac exerted a moderate effect towards the normalization of both COX isoforms in the liver, moderately increased the content of PGE2, and decreased - PGF2α and TXB2 without changing the level of PGI2. In serum, diclofenac reduced COX-1 level to subnormal values, and its effect on other biomarkers was similar to that in the liver, except for a moderate decrease in PGI2. Thus, diclofenac was inferior to etoricoxib, which normalized COX-1, COX-2, PGE2, and PGI2 in the liver and reduced the content of PGF2α and TXB2 in the liver to subnormal values. At the same time, in the blood serum, it decreased COX-1, COX-2, and PGE2 to subnormal values, normalized PGF2α, and PGI2, and significantly reduced TXB2. The opposite degree of intensity of the influence of diclofenac and etoricoxib on the cyclooxygenase pathway and body temperature indicates a dissociation of anti-inflammatory and frigoprotective activity. Inhibition of oxidative stress is not determinative for the frigoprotective activity of NSAIDs since diclofenac, despite the weaker influence on the content of 8-isoprostane in the liver, still exerts the maximum frigoprotective activity.

Modulating Gut Microbiota: An Emerging Approach in the Prevention and Treatment of Multiple Sclerosis.

Multiple sclerosis (MS) is a progressive neuromuscular disorder characterized by demyelination of neurons of the central nervous system (CNS). The pathogenesis of the disorder is described as an autoimmune attack targeting the myelin sheath of nerve cell axons in the CNS. Available treatments only reduce the risk of relapse, prolonging the remissions of neurological symptoms and halt the progression of the disorder. Among the new ways of targeting neurological disorders, including MS, there is modulation of gut microbiota since the link between gut microbiota has been rethought within the term gut-brain axis. Gut microbiota is known to help the body with essential functions such as vitamin production and positive regulation of immune, inflammatory, and metabolic pathways. High consumption of saturated fatty acids, gluten, salt, alcohol, artificial sweeteners, or antibiotics is the responsible factor for causing gut dysbiosis. The latter can lead to dysregulation of immune and inflammatory pathways, which eventually results in leaky gut syndrome, systemic inflammation, autoimmune reactions, and increased susceptibility to infections. In modern medicine, scientists have mostly focused on the modulation of gut microbiota in the development of novel and effective therapeutic strategies for numerous disorders, with probiotics and prebiotics being the most widely studied in this regard. Several pieces of evidence from preclinical and clinical studies have supported the positive impact of probiotic and/or prebiotic intake on gut microbiota and MS. This review aims to link gut dysbiosis with the development/progression of MS, and the potential of modulation of gut microbiota in the therapeutics of the disease.

The influence of oxonate-induced hyperuricemia and allopurinol on behavioral reactions of random-bred mice.

BACKGROUND: Purine metabolism specificity, namely the high level of uric acid in the blood, is considered to be significant in the appearance of intellectually-developed primates, as well as in later periods of human development, for personal activity and achievements and even for the formation of genius. Nowadays hyperuricemia is mostly associated with the pathogenesis of hypertension and metabolic syndrome. Its influence on the central nervous system is predominantly set aside. METHODS: The behavioral reactions of random-bred mice with uricase inhibition due to potassium oxonate or xanthine oxidase suppression with allopurinol for three weeks were investigated. RESULTS: Potassium oxonate reduced signs of anxiety in the elevated plus maze. A positive correlation appeared between latency to enter a dark arm and uricemia, so anxiety reduction can be associated with uric acid metabolism changes. Allopurinol reduced anxiety that was not related to the metabolic changes of uric acid, so the involvement of changes in uric acid precursor concentrations cannot be excluded. Potassium oxonate but not allopurinol reduced immobility in a tail suspension test. There was a tendency to increase the duration of swimming to exhaustion against the potassium oxonate background. At the same time, potassium oxonate reduced research activity in the combined open field test and increased the vegetative maintenance of behavioral responses. Allopurinol did not change the results of this test. CONCLUSIONS: A reduction in anxiety and depression level and a tendency to augment physical performance against the potassium oxonate background partly conform to the beneficial evolutionary role of hyperuricemia.