Analysis of KK1 compound effects on immunological and biochemical parameters in prenatally tobacco-exposed rat Wistar offspring

Active and passive tobacco smoking is one of the widespread low-toxicity factors affecting animals and humans. In previous studies, the authors investigated morphological and immunological parameters in passively smoke-exposed rats. The aim of our study was to continue research in this direction focusing on the effects of a synthetic KK1 peptide, a structural analogue of the ACTH primary sequence (15-18) (Acetyl-(D-Lys)-Lys-Arg-Arg-amide) with antioxidant and stress-protective properties, on the phagocytic activity of peritoneal macrophages and intensity of free-radical oxidation in the liver and blood serum. Immunological and biochemical parameters were assessed in 60 pups from tobacco smoke-exposed and non-exposed Wistar rats. The pregnant rats were subjected to tobacco smoke (8 hours a day, from 1^st to 20^th day of gestation). Control groups received saline, while experimental groups were administered KK1 (intranasally, at a dose of 40 μg/kg, five times during the 10-day period). 21 days postpartum, the little rats were evaluated for phagocytic indices, circulating immune complex levels (CIC), hepatic enzyme activity (alanine aminotransferase (ALT), aspartate aminotransferase (AST)), oxidative stress markers (malondialdehyde (MDA), diene conjugates (DC), and antioxidant enzymes (superoxide dismutase (SOD), catalase). The study has shown that prenatal tobacco smoke exposure in rat offspring was associated with reduced phagocytic activity, but elevated neutrophil metabolic activity, increased serum AST activity, activated free radical oxidation (elevated MDA, DC), along with suppression of endogenous antioxidant defense mechanisms (decreased SOD and catalase). Administration of the KK1 compound was associated with normalized phagocytic indices, reduced AST activity and restored antioxidant defenses. These findings support the opinion on antioxidant properties of KK1 under passive smoking conditions, highlighting its immunoprotective effects. The effects of KK1 compound may be associated with modulation of synaptic membrane fluidity, regulation of receptor functions, protein phosphorylation processes, and suppression of excessive cytokine synthesis. The observed reduction in free-radical oxidation products and enhancement of catalase activity align with existing evidence of KK1’s antioxidant and stress-protective efficacy. The KK1 compound has demonstrated antioxidant and immunoprotective effects by mitigating the adverse consequences of prenatal tobacco smoke exposure in rat offspring. These findings support its potential application in studies investigating the impact of low-toxicity environmental factors in experimental animal models.