Chukwuemeka R. Nwokocha

Comparative study on the efficacy of Allium sativum (garlic) in reducing some heavy metal accumulation in liver of wistar rats.

SCOPE Heavy metals are known to cause damage through indirect oxidative effects. This study was undertaken to compare the therapeutic efficacy and protective ability of garlic extracts on reducing toxicity induced by mercury, lead and cadmium in the liver. METHODS AND RESULTS Rats were fed with rat chow mixed with raw garlic (7% w/w) while mercury (10ppm), cadmium (200ppm) and lead (100ppm) were given in drinking water. Garlic was administered either at the same time with the metals (group 2), a week after exposure to heavy metals (group 3) or a week before heavy metal exposure (group 4) for 6weeks. The heavy metal accumulations in the liver were determined using AAS. The percentage protection showed a time-dependent effect and was significantly (P<0.01) higher for cadmium compared to mercury and lead-treated groups. Analysis between the groups showed that garlic treatment after exposure had a significantly (P<0.05) higher percentage protection when compared with other modes. CONCLUSION These results suggest that garlic offered more hepatoprotective effect to cadmium followed by mercury and least protection to lead at the selected dose of each metal in this study through the processes of uptake, assimilation and elimination of these metals.

Possible mechanisms of action of the aqueous extract of Artocarpus altilis (breadfruit) leaves in producing hypotension in normotensive Sprague-Dawley rats.

Context and objectives: Artocarpus altilis (Parkinson) Fosberg (Moraceae) (breadfruit) leaves are used as an antihypertensive remedy. We investigated the possible mechanisms of action of its aqueous extract and its effect on cytochromes P450 (CYP) enzyme activities. Materials and methods: Intravenous administration of an aqueous leaf extract (20.88–146.18 mg/kg) of A. altilis on mean arterial pressure and heart rate were recorded via cannulation of the carotid artery on anaesthetized normotensive Sprague–Dawley rats. Recordings of the contractile activity of the aortic rings to the extract (0.71–4.26 mg/mL) were studied using standard organ bath techniques. Inhibitions of human CYP3A4 and CYP2D6 enzyme activities were evaluated by means of a fluorometric assay in 96 well plates using heterologously expressed microsomes. Results: A. altilis caused significant (p < 0.05) hypotensive and bradycardiac responses unaffected by atropine (2 mg/kg) and mepyramine (5 mg/kg), but attenuated by propranolol (1 mg/kg) and N(G)-nitro-l-arginine methyl ester (5 mg/kg). The extract (0.71–4.26 mg/mL) significantly (p < 0.05) relaxed phenylephrine (10−9–10−4 M) and 80 mM KCl-induced contractions in endothelium intact and denuded aortic rings; and caused a significant (p < 0.05) rightward shift of the Ca2+ dose-response curves in Ca2+-free Kreb’s solution. Moderate inhibitions of cytochrome P450s (CYP3A4 and CYP2D6) enzyme activities with IC50 values of 0.695 ± 0.187 and 0.512 ± 0.131 mg/mL, respectively, were produced. Conclusion: A. altilis exhibits negative chronotropic and hypotensive effects through α-adrenoceptor and Ca2+ channel antagonism. Drug adversity effects are unlikely if the aqueous leaf extract is consumed with other medications reliant on CYP3A4 and CYP2D6 metabolism. This study thus provides scientific evidence for the use of the breadfruit in the treatment of hypertension.

Comparative study on the efficacy of Garcinia kola in reducing some heavy metal accumulation in liver of Wistar rats.

Garcinia kola is regarded as an antidote and anti-hepatotoxic agent. We examined its protection ability against mercury (Hg), lead (Pb) and cadmium (Cd) accumulation in the liver. The ground seed was mixed with rat feed (5%, w/w) and fed to rats while Hg (10 ppm), Cd (200 ppm) and Pb (100 ppm) was given in drinking water. Garcinia kola was administered either at the same time with the metals (group 2), a week after exposure to heavy metals (group 3) or given a week before heavy metal exposure (group 4) for six weeks. The heavy metal accumulations in the liver were determined using AAS. Garcinia kola could not reverse the weight reduction in the heavy metal exposed groups although it offers more protection and aid greater elimination of heavy metals from the liver. There was a significant (P<0.01) increase in protection by Garcinia kola to Cd (72.4%) and Pb (56.2%) accumulation when compared to Hg (40%) at week 2 which was significantly (P<0.01) decreased at week 4 when compared to week 2. At week 6, the percentage protection to both Hg (64.2%) and Cd (62.2%) were comparable to each other while protection to Pb (49.9%) accumulation was significantly (P<0.01) reduced. The percentage protection was time-dependent in some groups but treatment during and after the exposure provided a greater protection. Garcinia kola has the highest hepatoprotective effect to Cd followed by Hg and least protection against Pb toxicity in rats and its administration is beneficial in reducing heavy metal accumulation in the liver.

Comparative analysis on the effect of Lycopersicon esculentum (tomato) in reducing cadmium, mercury and lead accumulation in liver

SCOPE L. esculentum (tomato) contain compounds with anti-oxidant and anti-inflammatory properties, able to synthesize metal chelating proteins. We examined the ability of fruit extract to protect against mercury (Hg), lead (Pb) and cadmium (Cd) accumulation in the liver. METHODS AND RESULTS Rats were fed on tomato mixed with rat chow (10% w/w), while Hg (10 ppm), Cd (200 ppm) and Pb (100 ppm) was given in drinking water. Tomato was administered together with the metals (group 2), a week after exposure (group 3) or a week before metal exposure (group 4) for a period of six weeks. The metal accumulations in the liver were determined using AAS. There was a significant (P<0.05) increase in protection by tomato to Cd and Hg accumulation but not to Pb (P<0.05) in weeks 2 and 4 for groups 2 and 3. The protective ability was significantly (P<0.05) increased for Pb in group 4, but was less comparable to Cd and Hg. CONCLUSION Tomato reduces uptake while enhancing the elimination of these metals in a time dependent manner. The highest hepatoprotective effect was to Cd followed by Hg and least to Pb. Its administration is beneficial in reducing heavy metal accumulation in the liver.

Possible mechanisms of action of the hypotensive effect of Annona muricata (soursop) in normotensive Sprague–Dawley rats

Context: Annona muricata Linn (Annonaceae) (soursop) is a food plant reported to have antihypertensive properties. Objective: We investigated the blood pressure reducing effect of its aqueous leaf extract and the possible mechanisms that may be responsible. Methods: Intravenous administration of an aqueous leaf extract (9.17–48.5 mg/kg) of A. muricata on the mean arterial pressure and heart rate were recorded invasively on anaesthetized, normotensive Sprague–Dawley rats. Contractile responses of rat aortic rings to the extract (0.5–4.0 mg/mL) were studied using standard organ bath techniques. Results: A. muricata (9.17–48.5 mg/kg) caused significant (p < 0.05) dose-dependent reduction in blood pressure without affecting the heart rates. The hypotensive effects were unaffected by atropine (2 mg/kg), mepyramine (5 mg/kg), propranolol (1 mg/kg) and L-NAME (5 mg/kg). A. muricata leaf aqueous extract significantly (p < 0.05) relaxed phenylephrine (10−9–10−4 M) and 80 mM KCl induced contractions in endothelium intact and denuded aortic rings; and caused a significant (p < 0.05) rightward shift of the Ca2+ dose response curves in Ca2+-free Kreb’s solution containing 0.1 mM EGTA. Conclusions: The hypotensive effects of A. muricata are not mediated through muscarinic, histaminergic, adrenergic and nitric oxide pathways, but through peripheral mechanisms involving antagonism of Ca2+.

In vivo distribution of lead in male and female rats after intraperitoneal and oral administration

The resultant effects of lead exposure are seen in almost all the systems of the body and results in toxicity to many organs. Since toxicity depends on its degree of uptake, distribution and metabolism, the authors investigated the differential uptake, accumulation and distribution of lead in organs of males and female Wistar rats following various routes of administration. Group 1 served as control male and control female; group 2 males and females received 5 mg/kg body weight of lead intraperitoneally for 8 days while group 3 males and female rats were administered drinking water containing 100 ppm of lead acetate for 18 days. Tissues were collected for analysis of the lead content using atomic absorption spectroscopy. The relative retention of lead by the tissues was greater in rats exposed to lead by the i.p. route varying in the order of accumulation / uptake in males as lungs > spleen > stomach > kidney > blood > heart and in females as spleen > stomach > heart > kidney > blood > lungs (i.p. route) and (oral route) as for males kidney > lungs > stomach > blood > heart > spleen, and females as kidney > lungs > stomach > blood > heart > spleen. Male Wistar rats showed more accumulation with oral exposure in lungs, spleen and blood with values for kidney and stomach being significantly (p < 0.05) higher when compared with females. Female Wistar rats showed more accumulation with i.p. exposure for spleen and stomach tissues while values for the heart was significantly (p < 0.05) higher than the males. Our findings suggest that lead retention and the organ distribution varied depending upon the sex and route of lead administration.

Possible Mechanism of Action of the Hypotensive Effect of Peperomia pellucida and Interactions between Human Cytochrome P450 Enzymes

Background: Peperomia pellucida is used as a medicinal plant and as an antihypertensive remedy. We investigated the possible mechanism of this action and its impact on cytochrome P450 (CYP) enzyme activity. Methods: Mean arterial pressure and heart rate were recorded via cannulation of the carotid artery on anaesthetized, normotensive Sprague-Dawley rats following intravenous administration of Peperomia pellucida aqueous (10-30 mg/ kg) plant extract (PPAE). Recordings of the contractile activity of the aortic rings to the extract (1.9-8.6 mg/ml) were done using standard organ bath techniques. Impact on CYP3A4 and CYP2D6 enzyme activities was investigated using human liver and heterologously expressed microsomes. Results: We observed a dose-dependent reduction in systolic, diastolic, MAP and HR. Pre-treatment with atropine (2 mg/kg) and propranolol (1 mg/kg) but not mepyramine (2 mg/kg) significantly (p<0.05) reduced the hypotensive and negative chronotropic activities caused by the extract, while L-NAME (5 mg/kg) completely abolished it. PPAE significantly (p<0.05) relaxed the phenylephrine (10 -9 -10 -4 M) and KCl- induced contractions and displayed moderate inhibition of CYP3A4 enzyme activity with IC50 values of 0.466 ± 0.126 mg/mL and 0.153 ± 0.054 mg/mL, respectively using heterogenously expressed CYP3A4 and human liver microsomes (HLMs) Conclusion: Results suggest dose-dependent hypotensive, bradycardic and vasorelaxant effects of PPAE are mediated through Nitric oxide-dependent mechanisms. The impact on CYPs enzyme activities indicate unlikely adverse drug effect when Peperomia pellucida is consumed with other medications reliant on CYP3A4 metabolism.

Comparative study on the hepatoprotection to heavy metals of Zingiber officinale.

Context: Zingiber officinale (Zingiberaceae) is a herb used for culinary and therapeutic purposes due to its anti-inflammatory and antioxidant potentials. Objectives: We examined its protective ability against mercury (Hg), lead (Pb) and cadmium (Cd) accumulation in the liver. Materials & Methods: Ground Zingiber officinale (7%, w/w of feed) was administered to rats either at the same time with the exposure ofheavy metals (group 2), a week after exposure to heavy metals (group 3) or given a week before heavy metal exposure (group 4) for six weeks. Animals were exposed to either of Hg (10 ppm), Cd (200 ppm) and Pb (100 ppm) in drinking water. The heavy metal accumulations in the liver were determined using AAS. Results: Weight losses induced by these metals were not reversed by Zingiber officinale administration. There was a significant (P<0.01) increase in protection to Pb (97%) and Cd (63%) accumulation when compared to Hg (32%) at week 2. The protective ability was significantly (P<0.01) decreased at week 4 when compared to week 2 for Cd and Pb but not to Hg in groups 3 (50%) and 4 (52%). At week 6, hepatoprotection to Hg (44%) and Cd (85%) was significantly (P<0.01) different but not to Pb which was only significant (P<0.05) in week 2 of treatment for all groups. Discussion and Conclusion: Zingiber officinale affected the bioavailability, elimination and uptake of these metals in a time-dependent way with highest beneficial reducing effect to Cd followed by Hg and least protection to Pb in the liver.

Comparative analysis on the effect of palm oil (Elaeis guineensis) in reducing cadmium and lead accumulation in liver of Wistar rats

Context: Palm oil from Elaeis guineensis is an edible nutrient substance with anti-inflammatory and antioxidant properties. We examined its protective effect against lead (Pb) and cadmium (Cd) accumulation in the liver. Materials and Methods: 12% w/w of palm oil (PO) in rat chow concentrate was fed to rats exposed to Cd (200ppm) and Pb (100ppm) in drinking water at different feeding regimens. PO was administered either at the same time with the metals (group 2), post-treatment after exposure (group 3) or pre-treatment before exposure (group 4) for six weeks. The heavy metal accumulations in the liver were determined using AAS. Results: Weight losses induced by these metals were significantly (P<0.05) reversed by PO administration. Analysis among the groups showed that post-treatment group had a significant (P<0.05) higher percentage protection to Cd, but same time treatment for Pb (P<0.05) when compared with other groups. The protective ability to PO was only significantly (P<0.05) increased for Pb at week 2, but showed a time-dependent significant (P<0.05) increase for Cd across all treatment regimens. Conclusion: PO is beneficial in reducing metal accumulation in the liver and has a higher hepatoprotective effect to Cd compared to Pb at the selected doses by possibly affecting the processes of uptake, assimilation and elimination of these metals.

Gastric Ulceration in Diabetes Mellitus: Protective Role of Vitamin C

The effect of vitamin C administration on gastric acid secretion and ulcer in diabetic rats was studied. Vitamin C (200 mg/kg b.w.) was administered to both streptozotocin-induced diabetic and control groups orally for 28 days. Gastric acid secretion was measured and ulcer was induced using ethanol. Histological changes were observed in the stomach. Basal and stimulated acid secretion in diabetic control rat was significantly (P < 0.01) decreased when compared to vitamin C-treated diabetic group and control. Administration of vitamin C significantly (P < 0.05) increased the histamine-stimulated gastric acid secretion in diabetics than control while reduction in gastric secretion by ranitidine was similar compared with control. Vitamin C treatment significantly (P < 0.05) reduced ulcer index in diabetic group and increased mucus weight when compared with diabetic group which was also confirmed with photomicrographs. The mean body weight of diabetic rats treated with vitamin C was comparable to the control. The blood glucose level was significantly (P < 0.01) reduced in diabetic group given vitamin C (8.9 ± 1.8 mMol/L) compared to the diabetic control (32.2 ± 2.1 g). It is concluded that vitamin C is beneficial in improving gastric acid secretion and protects against ulceration in streptozotocin-induced diabetes mellitus in rats due to its antioxidant potential.