ABSTRACT
Objective: To evaluate the protective effect of the coconut oil nanoemulsion against methotrexate-induced hepatotoxicity and nephrotoxicity in Ehrlich ascites carcinoma-bearing Swiss albino mice. Methods: Forty mice were divided into four groups. Group I served as the untreated Ehrlich ascites carcinoma-bearing mice while Ehrlich ascites carcinoma-bearing mice in groups II-IV received an intraperitoneal injection of 0.2 mL/kg coconut oil nanoemulsion, 20 mg/kg methotrexate as well as 0.2 mL/kg coconut oil nanoemulsion mixed with 20 mg/kg methotrexate, respectively. The toxicities of the treatments were assessed by determining the complete blood count, performing the serum analysis for liver and kidney functions, evaluating the oxidative status and visualizing histological changes in the liver and kidney tissues. Results: Treatment with methotrexate and coconut oil nanoemulsion markedly diminished the liver parameters including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein, direct bilirubin and total bilirubin which were raised by methotrexate treatment (P < 0.05). Similarly, creatinine and blood urea nitrogen, as the indicators of kidney function, were dramatically lowered in the combination treatment group compared to the methotrexate group (P < 0.05). In addition, treatment with methotrexate and coconut oil nanoemulsion reduced the malondialdehyde and increased catalase, glutathione reductase and superoxide dismutase, in the liver and kidney tissues (P < 0.05). The treatment with methotrexate and coconut oil nanoemulsion reduced white blood cell count and increased the hemoglobin amount (P < 0.05), but did not cause any change in platelets and red blood cell count. Conclusions: Coconut oil nanoemulsion as a nanocarrier has great potential in reducing the adverse side effects induced by methotrexate.
ABSTRACT
Prostaglandin E2 [PGE2] is increased in inflammation and modulated intestinal peristalsis in the small intestine. However, the receptor mechanisms involved during parasitic inflammation are unknown. The aim of the present study was to investigate the role of EP2 receptors involved in the mechanisms underlying post-inflammatory changes during inflammation. Experiments were performed in male Swiss mice 4- and 8-wks following infection with S. mansoni and the results compared to those of uninfected control mice. Jejunal contraction was assessed using a modified Trendelenburg type preparation to study motor complexes [MCs]. Infection had great effects on jejunal motility that reflected by an increase of amplitude and a decrease of interval between MCs. EP2 receptor agonist AH 13205 [lO micro M] produced a significant inhibition of MCs which appeared as a decrease in amplitude and an increase in intervals in control, 4- and 8-wks infected animals. EP, and EP2 receptors antagonist AH6809 [30 micro M] attenuated intestinal peristalsis by a significant inhibition followed by contraction in control, 4- and 8-wks infected animals. In the presence of EP2 receptor antagonist AH6809, EP2 receptor agonist AH 13205 failed to alter the peristaltic motor activity in control, 4- and 8-wks infected jejunum. These data demonstrated temporal differences in motor function during the intensity of inflammation. EP2 receptor plays a potential role in modulating jejunal motility of control animals and altered motility triggered by parasitic inflammation