Significance: We identified a novel function of cytoglobin (Cygb) as an efficient superoxide dismutase (SOD) with a high–bimolecular dismutation rate on the order of 10 ⁸ M ⁻¹ ⋅ s ⁻¹ . It is the first Fe-centered SOD identified in mammalian cells and the only member of the globin family shown to have potent SOD activity. This SOD function of Cygb may serve to explain the prior reports of its antioxidative activity and the toxicities and disease seen with its genetic deletion, including the increased incidence of tumors. Combined with its potent NO dioxygenase activity, Cygb would be highly effective in decreasing both O ₂ ^•− and NO levels, serving to decrease the formation of peroxynitrite and secondary oxidative injury.

Cisplatin (CP) is one of the most potent anti-cancer drugs used against different types of cancer. Its use is limited due to its nephrotoxicity. This study is aimed to evaluate the role of a super oxide dismutase (SOD) mimetic agent, tempol, in protection against CP nephrotoxicity in rats. Animals were divided into four groups: Group-1: Normal control group, Group-2: CP group (single dose of CP 6 mg/kg, i.p.), Group-3 and Group-4: Tempol-treated groups (50 mg/kg p.o. and 100 mg/kg p.o. respectively) daily for a week before CP injection and continued for an additional four days after CP injection. Urine and blood samples were collected for the evaluation of kidney function including serum creatinine, BUN, cystatin-c, and creatinine clearance. In addition, western blotting was used to determine urine lipocalin-2 content. Furthermore, kidney tissue was collected for the determination of oxidative stress markers, caspase-3 expression, and histopathological examination. We noticed that both doses of tempol significantly improved kidney function, which was deteriorated by CP injection. Tempol significantly elevated kidney glutathione (GSH) content and SOD activity, and decreased kidney lipid peroxidation and NOx production. Tempol also significantly decreased kidney caspase-3 expression which was elevated by CP toxicity. Thus, we conclude that tempol can protect against CP nephrotoxicity. We noticed that both doses of tempol are effective in ameliorating CP-nephrotoxicity.

Ulcerative colitis (UC) is a chronic inflammatory life-threatening and premalignant disorder with no cure that even might end up with surgical removal of a large section or even all of the colon. It is characterized by relapsing-remitting courses of intestinal inflammation and mucosal damage in which oxidative stress and exaggerated inflammatory response play a significant role. Most of the current medications to maintain remission are symptomatic and have many adverse reactions. Therefore, the potential for improved management of patients with UC continues to increase. Yet, the benefits of using the antiarthritic agent diacetylrhein to counteract inflammation in UC are still obscure. Hence, our study was designed to explore its potential role in UC using a model of dextran sodium sulfate-induced acute colitis in rats. Our results revealed that diacetylrhein targeted the NLRP3 and inhibited the inflammasome assembly. Consequently, caspase-1 activity and the inflammatory cytokines IL-1β and IL-18 were inhibited leading to a curbed pyroptosis process. Additionally, diacetylrhein revealed a significant antiapoptotic potential as revealed by the levels of pro-apoptotic and anti-apoptotic proteins. Concomitant to these effects, diacetylrhein also interrupted NFκB signals leading to improved microscopic features of inflamed colon and decreased colon weight to length ratio, indices of disease activity, and macroscopic damage. Additionally, a reduction in the myeloperoxidase activity, IL-6, and TGF-β alongside an increase in the gene expression of Ocln and ZO-1 were detected. To conclude diacetylrhein showed a significant antioxidant and anti-inflammatory potential and therefore might represent a promising agent in the management of acute UC.