Modulation of L-arginine-induced acute pancreatitis by meloxicam and/or L-carnitine in rats

Abstract

Background: Acute pancreatitis (AP) is an inflammatory disease, where oxidative stress, subsequently inflammatory mediators activation play a pivotal role. Currently, no definite treatment exists and therapy is mainly supportive that directed to inhibit local pancreatic injury and systemic inflammatory complications. This study is presented to explore whether anti-inflammatory and/or antioxidant drug could ameliorate L-arginine-induced AP. Methods: Rats were sub-grouped randomly into five groups. Control group, AP was provoked by a single intraperitoneal injection of L-arginine (250 mg/100g), rat treated with meloxicam (4 mg/kg, IP), animals treated with L-carnitine (500 mg/kg, IP), and rats were treated with both meloxicam and L-carnitine. All treatments were once daily for 7 consecutive days and started 1 hr later after L-arginine administration. Serum and tissues samples were prepared for biochemical analysis. Histopathological examination for the other pancreatic tissues was done. Results: L-arginine significantly elevated serum activity of amylase and lipase enzymes, while notably reduced serum calcium level. Moreover, L-arginine markedly increased the pancreatic tissues content of tumor necrosis factor-α, malondialdehyde, and nitric oxide. In addition, L-arginine significantly increased pancreatic activity of myeloperoxidase, while markedly depleted glutathione level. Treatment with either meloxicam or L-carnitine significantly attenuated L-arginine-induced biochemical changes. On the other hand, co-administration of both meloxicam and carnitine has an ameliorative effect greater than each drug alone. Conclusion: Treatment with both meloxicam and L-carnitine is a more effective than each of them alone which is attributed to augmentation their antioxidant, anti-inflammatory effects.

Comparative Histological Study on The Effect of Bone Marrow-Derived Mesenchymal Stem Cells Versus Wheat Germ Oil on Acute Pancreatitis in A Rat Model

“…The current study induced experimental AP in rats by using a single I.P injection of L-arginine in a dose of 250 mg/100g body weight. This is in accordance with El-Rahman et al (2011) [21] and Hasan et al (2015) [22] . L-arginine produces biochemical and histological changes like that of human AP [23] .…”

“…L-arginine produces biochemical and histological changes like that of human AP [23] . It distorts the membranes of zymogen granules and release their enzymes to the interstitium causing inflammation [22] . Time of scarification was chosen according to Moreira et al, 2011 [24] who stated that peak histological changes were observed around 72 h after induction of AP.…”

Comparing the preventive effect of sodium hydrosulfide, leptin, and curcumin against L-arginine induced acute pancreatitis in rats: role of corticosterone and inducible nitric oxide synthase

“…This could result in formation of MDA, which can activate nuclear factor-kappa B (NF-κB) with a subsequent up regulation of various inflammatory cytokines, which has been found by Yenicerioglu et al (2013). Hasan et al (2015) have also reported that the excess ROS could attack lipids and proteins in the membranes of zymogen granules in pancreas which led to infiltration of great amount of digestive enzymes into pancreatic tissues with subsequent autodigestion and elevation of pancreatic enzymes that is in accordance with our study results. Furthermore, Mirmalek et al (2016) have shown that activation of granulocytes and other proinflammatory mediators is regulated by TNF-α, which activates intracellular protease (trypsinogen) and thus cellular necrosis.…”

“…An elevated level of NO could be ascribed to induction of iNOS that was evoked by inflammatory cytokines. NO reacts with superoxide anion to form peroxynitrite that can react directly with lipid, protein and DNA resulting in cellular dysfunction and tissue injury what has been demonstrated in many studies (Biradar and Veeresh 2013;Al-Malki 2015;Hasan et al 2015;Aziz et al 2017).…”

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“…This results in releasing the digestive enzymes, cellular proteins, and increased levels of inflammatory mediators. 5 Honeybees products include numerous substances such as bee venom, bee propolis, bee pollen, and royal jelly. They are known to have many medicinal and health-promoting properties.…”