Effects of Melatonin and Flavonoid-Rich Fractions of Chromolaena odorata on the Alteration of Proinflammatory Cytokines and Nitric Oxide Induced by Aflatoxin B1 in the Gastric Mucosa of Wistar Rats.

In this study, we investigated serum interleukin-1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) after ingestion of aflatoxin B1 (AFB1) in rats. We also studied the effects of nitric oxide (NO) on the stomach after consumption of AFB1. Therefore, we hypothesized that a standard anti-inflammatory agent-melatonin (MEL), and the flavonoid-rich fractions from Chromolaena odorata (FRFC) could counteract the deleterious effects of IL-1ß, TNF-α, and NO after consumption of AFB1. Thirty-five Wistar rats (211.86 ± 27.23 g) were randomly selected into 5 groups, with 7 rats in each group. Group A (control); all rats in groups B, C, D, and E received 2.5 mg/kg AFB1 each orally on day 5, whereas those of groups C, D, and E received oral administration of 10 mg/kg MEL, 50 mg/kg FRFC1, and 100 mg/kg FRFC2, respectively, for 7 days. All of them were killed on the 8th day, 24 h after last treatment. Serum samples were analyzed for IL-1ß and TNF-α, whereas stomach tissue was evaluated for NO level. Significant (P < 0.5) increase in serum IL-1ß and TNF-α in rats given AFB1 only was recorded when compared with those in the control group. Conversely, we observed significant reduction in serum IL-1ß and TNF-α in all the groups that received MEL, FRFC1, and FRFC2 after pretreatment with AFB1 when compared with those that were given AFB1 only. In addition, there was a significant increase in NO in rats given AFB1 only when compared with control, whereas reduction in NO was significant in the groups C, D, and E that were given MEL, FRFC1, and FRFC2, respectively, when compared with AFB1 group. MEL and FRFC may be responsible for the prevention of increased gastric mucosal NO and inflammatory effects of proinflammatory cytokines induced by AFB1.

Preconditioning with Azadirachta indica ameliorates cardiorenal dysfunction through reduction in oxidative stress and extracellular signal regulated protein kinase signalling.

BACKGROUND: Azadirachta indica is widely distributed in Africa, Asia and other tropical parts of the world. A. indica (AI) is traditionally used for the treatment of several conditions including cancer, hypertension, heart diseases and skin disorders. Intestinal ischaemia-reperfusion is a common pathway for many diseases and may lead to multiple organ dysfunction syndrome and death. OBJECTIVE: In this study, we investigated the ameliorative effects of AI on intestinal ischaemia-reperfusion injury-induced cardiorenal dysfunction. MATERIALS AND METHODS: Sixty rats were divided into 6 groups; each containing 10. Corn oil was orally administered to group A (control) rats for 7 days without intestinal ischaemia-reperfusion injury. Group B underwent intestinal ischaemia-reperfusion injury (IIRI) without any pre-treatment. Groups C, D, E and F were pre-treated orally for 7 days with 100 mg/kg AI (100 and (200 mg/kg) vitamin C (100 and 200 mg/kg) respectively and thereafter underwent IIRI on the 8th day. RESULTS: The cardiac and renal hydrogen peroxide increased significantly whereas serum xanthine oxidase and myeloperoxidase levels were significantly elevated (p < 0.05) in IIRI only when compared to the control. The cardiac and renal reduced glutathione, glutathione peroxidase, protein thiol, non-protein thiol and serum nitric oxide (NO) decreased (p < 0.05) significantly following IIRI. Immunohistochemical evaluation of cardiac and renal tissues showed reduced expressions of the extracellular signal regulated kinase (ERK1/2) in rats with IIRI only. However, pre-treatment with A. indica and vitamin C significantly reduced markers of oxidative stress and inflammation together with improvement in antioxidant status. Also, reduced serum NO level was normalised in rats pre-treated with A. indica and vitamin C with concomitant higher expressions of cardiac and renal ERK1/2. CONCLUSIONS: Together, A. indica and vitamin C prevented IRI-induced cardiorenal dysfunction via reduction in oxidative stress, improvement in antioxidant defence system and increase in the ERK1/2 expressions. Therefore, A. indica can be a useful chemopreventive agent in the prevention and treatment of conditions associated with intestinal ischaemia-reperfusion injury.

Changes in serum cytokine levels, hepatic and intestinal morphology in aflatoxin B1-induced injury: modulatory roles of melatonin and flavonoid-rich fractions from Chromolena odorata.

Aflatoxins are known to produce chronic carcinogenic, mutagenic, and teratogenic effects, as well as acute inflammatory effects, especially in the gastrointestinal tract. The potentials of the flavonoid-rich extract from Chromolena odorata (FCO) and melatonin (a standard anti-oxidant and anti-inflammatory agent) against aflatoxin B1 (AFB1)-induced alterations in pro-inflammatory cytokine levels and morphology of liver and small intestines were evaluated in this study. We utilized Wistar albino rats (200-230 g) randomly divided into five groups made up of group A, control rats; group B, rats given AFB1 (2.5 mg/kg, intraperitoneal) twice on days 5 and 7; rats in groups C, D, and E were treated with melatonin (10 mg/kg, intraperitoneal) or oral doses of FCO1 (50 mg/kg) and FCO2 (100 mg/kg) for 7 days, respectively, along with AFB1 injection on days 5 and 7. Serum levels of interleukin 1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) were determined using commercial ELISA kits and histopathological evaluation of the liver, duodenum, and ileum were also carried out. We observed significant elevation (p < 0.05) in serum IL-1ß correlating with hemorrhages and leucocytic and lymphocytic infiltration in the liver and intestines as evidences of an acute inflammatory response to AFB1 administration. All treatments yielded significant reduction (p < 0.05) in IL-1ß levels, although TNF-α levels were not significantly altered in all rats that received AFB1, irrespective of the treatments. Melatonin and FCO2 produced considerable protection of hepatic tissues, although melatonin was not quite effective in protecting the intestinal lesions. Our findings suggest a modulation of cytokine expression that may, in part, be responsible for the abilities of C. odorata or melatonin in amelioration of hepatic and intestinal lesions associated with aflatoxin B1 injury.