Mito-TEMPO improved L-Arginine- induced acute pancreatitis in rats via TLR-4/ NF-кB/ NLRP3 inflammasome downregulation and antioxidant properties

Abstract

Background: Acute pancreatitis (AP) is a globally significant disease with increasing incidence and prevalence especially in the western world. It has severe complications such as pseudocyst, infection, renal failure, breathing problems, diabetes, malnutrition and chronic pancreatitis. Chronic pancreatitis can lead to pancreatic cancer which is one of the worst types of cancer. Up till now, there is no licensed specific treatment for AP. Objective: This study investigated the therapeutic effects of Mito-TEMPO in the treatment of L-Arginine induced acute pancreatitis in rats besides a possible involved mechanistic pathway. Materials and Methods: Rats randomly allocated into 3 groups: (1) control (received normal saline), (2) L-Arginine treated (300mg/100gm, i.p once) & (3) L-Arginine+Mito-TEMPO treated (0.7mg/kg/ day, i.p for 7 days). After 7 days from AP induction, serum amylase & lipase, pancreatic inflammatory mediators "toll-like receptor-4 (TLR-4), nuclear factor kappa-B (NF-кB), NLRP3 inflammasome, caspase-1, interleukin-1 beta (IL-1B)", oxidative parameters "malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NO), reduced glutathione (GSH)", an apoptotic marker "caspase-3" & pancreatic histopathological changes were estimated for all rats.Results: L-Arginine induced AP was evidenced by elevation of serum amylase & lipase, pancreatic inflammatory mediators "TLR-4, NF-кB, NLRP3 inflammasome, caspase-1, IL-1B", oxidative parameters "MDA, MPO, NO", the apoptotic marker "caspase-3" and infiltration of inflammatory cells proved through hematoxylin & eosin stain alongside with the reduction of GSH content. All these harmful effects were improved significantly after the administration of Mito-TEMPO. Conclusion: Mito-TEMPO can be introduced as a new therapy for the treatment of acute pancreatitis due to its anti-inflammatory and antioxidant effects.

Biochemical and histopathological changes of L-Arginine experimentally induced acute pancreatitis in male albino rats.

“…Observed typical acinar damage and inflammation were confirmed by a serum amylase level elevation (Amy et al, 2014;Ali et al,2020). Fawzy et al, 2021 reported that acute pancreatitis showed inflammation with lobular atrophy, apoptosis and vacuolar degeneration of acinar cells. Non-significant differences in the serum glucose levels were detected in the tested groups in the comparison with the control group due to using of only a single dose of L-arginine that induced mild acute pancreatitis without B cell injury.…”

“…Furthermore, MDA and NO were elevated in AP, whereas SOD activity and GSH levels were lowered. In addition, Fawzy et al, (2021) discovered that L-arginine promoted AP in rats via increasing serum amylase and lipase levels. The ALT and AST levels were strongly connected with the severity of pancreatitis, and they return to normal when pancreatitis is resolved (Kanwal et al, 2021).…”