Vincamine, an active constituent of Vinca rosea ameliorates experimentally induced acute lung injury in Swiss albino mice through modulation of Nrf-2/NF-κB signaling cascade.

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is one of the leading pulmonary inflammatory disorders causing significant morbidity and mortality. Vincamine is a novel phytochemical with promising anti-inflammatory properties. In the current work, the protective effect of vincamine was studied in vitro (Raw 264.7 macrophages) and in vivo against lipopolysaccharide (LPS) induced ALI in Swiss albino mice. Vincamine significantly reduced nitrite and TNF-α release from the LPS stimulated macrophages and increased the levels of IL-10, indicating potent anti-inflammatory effects. It was observed that vincamine at the dose of 40 mg/kg, significantly reduced LPS induced inflammatory cell count in blood and in bronchoalveolar lavage (BAL) fluid. Further, vincamine exerted potent suppression of inflammation by reducing the expression of proinflammatory cytokines, while significantly increased (p < 0.001) the expression of anti-inflammatory cytokine (IL-10 and IL-22). Interestingly, histological changes were reversed in vincamine treated groups in a dose-dependent manner. Immunohistochemical analysis revealed significantly enhanced expression of NF-κB, TNF-α and COX-2 while reduced expression of Nrf-2 in disease control group, which were significantly (p < 0.001) ameliorated by vincamine. We, to the best of our knowledge, report for the first time that vincamine possesses protective potential against LPS induced inflammation and oxidative stress, possibly by inhibiting the NF-κB cascade, while positively regulating the Nrf-2 pathway. These findings are of potential relevance for COVID-19 management concerning the fact that lung injury and ARDS are its critical features.

Protective role of N-Acetyl L-Cysteine against reproductive toxicity due to interaction of lead and cadmium in male Wistar rats.

INTRODUCTION: One of the target organs of heavy metals is testis and many authors proposed that oxidative stress could be responsible to induce their toxicity. An experimental study was conducted to evaluate the molecular mechanisms of lead (Pb) and cadmium (Cd) toxicity, their toxicodynamic interaction and to evaluate therapeutic potential of N-Acetyl L-cysteine (NAC) against the reproductive toxicity in male Wistar rats. MATERIAL AND METHODS: rats were randomly divided into 8 groups comprising of 6 rats in each. Group 1 and 2 were syam and NAC control, Group 3, 4 and 5 were kept as toxic control groups such as lead, cadmium and lead + cadmium respectively, where as Group 6, 7 and 8 were therapeutic groups with NAC. The experiment scheduled for 3 months. Body weights, anti-oxidant profile (GSH, GST, TBARS and protein carbonyls) in testis, testis weight, testicular LDH, sperm count and histopathology were conducted. And also, interaction of Pb and Cd with zinc (Zn) and copper (Cu) in testis was assessed. RESULTS: The present study revealed significant alterations in body weights, anti-oxidant profile, weights of testes, testicular LDH, sperm count, and concentration of Zn and Cu in toxic control groups 3, 4 and 5 as compared to control and NAC-treated groups. The toxic combination (Pb+Cd) group 5 showed significant alterations in protein carbonyls, GST levels and testicular LDH as compared to Pb and Cd alone administered groups and these results are substantiated with marked changes in the histopathology. All the NAC-treated groups revealed significant improvement in all the parameters. CONCLUSION: The results of the investigation revealed that Pb, Cd and their combination induces toxicity to the biological system due to the excess generation of free radicals and impairment of anti-oxidant defenses. Toxic effects were more pronounced in the group that received a combination of Pb and Cd, suggesting positive toxicodynamic interaction. Use of NAC countered the adverse effects of Pb and Cd induced toxicity to a major extent suggesting its anti-oxidant potential owing to replenishment of tissue pool of GSH. Further, NAC administration reduced the extent of accumulation of Pb and Cd in various tissues.