Influence of Amodiaquine Treatment on Microsomal Lipid Peroxidation and Antioxidant Defense Systems of Rats

Abstract

Abstract:The effects of single and multiple doses amodiaquine treatment on enzymatic and non-enzymatic antioxidant profiles and hepatic microsomal lipid peroxidation were investigated in rats. Treatment of rats with 10 mg/kg (single dose) amodiaquine resulted in 10% and 63% increases, respectively in the activities of liver superoxide dismutase and glutathione peroxidase (P∞0.01), while the activity of liver catalase was significantly reduced by 26% compared to control. The levels of serum vitamins A, C and b-carotene were lowered following amodiaquine treatment. Following multiple dose (10 mg/ kg for 4 consecutive days) amodiaquine treatment, activities of superoxide dismutase and glutathione peroxidase were increased by 30% and 133% respectively while catalase activity was decreased by 45%. Similarly, serum vitamins A, C and b-carotene levels were markedly decreased. In the single dose study, the levels of malondialdehyde and the activity of glutathione S-transferase were increased by 15% and 44% respectively while the reduced glutathione was decreased by 25% compared to control. Malondialdehyde level was highly increased (P∞0.001) by 71% following multiple amodiaquine treatment. Reduced glutathione was decreased by 55% and unlike in the single dose study, activity of glutathione Stransferase was decreased by 60% compared to control. The activities of serum aspartate amino transferase, alanine amino transferase, ornithine carbamyl transferase and g-glutamyl transferase were significantly increased by both single and multiple doses of amodiaquine treatment (P∞0.01). The alteration in enzymatic and non-enzymatic antioxidant defense system, increase in lipid peroxidation and increase in the activities of serum enzymes following amodiaquine treatment suggests damage to the liver and could subject the organ to further oxidative stress. The relevance of this to continuous exposure to amodiaquine therapy should be considered.

Protective effect of α‐lipoic acid against chloroquine‐induced hepatotoxicity in rats

“…This was confirmed by the study of Dass and Shah (2000) in which a marked elevation of transaminase levels was reported. Other antimalarials -amodiaquine (Farombi, 2000) and quinine (Debra and Megan, 1999) -were also reported to induce hepatic damage.…”

The effect of administration of amodiaquine on some Parameters of neurobehaviour of wistar rats

“…SA postures are "risk-assessment" behaviour which indicate that the animal is hesitant to move from its present location to the new position (Blanchard et al, 2001), and thus high frequencies of these activities indicates high level of anxiety. AQ causes lipid peroxidation and induced agranulocytosis (Maggs et al, 1988;Farombi, 2000). These had earlier been reported to result in agitation, aggressiveness, confusion, personality changes and psychotic symptoms in chronic doses (Tester-Dalderup, 1984) and involuntary movements in acute usage (Salako, 1984).…”

“…This has been implicated in lipid peroxidation (Maggs et al, 1988;Farombi, 2000). Peroxidation of lipid is responsible for damage to tissue in vivo (Mayes, 2000).…”

Cytotoxicity of chloroquine in isolated rat hepatocytes

“…Other antimalaria agentsamodiaquine (Farombi, 2000) and quinine (Debra and Megan, 1999) -were also reported to induce hepatic damage. Farombi and Emerole (1998) reported that CQ increased the cholesterol/phospholipids ratio in microsomes, thereby disrupting the membrane fluidity and leading to an alteration in membrane function.…”