Regulated rutin co-administration reverses mitochondrial-mediated apoptosis in Plasmodium berghei-infected mice

Malarial infection causes apoptosis in hepatocytes. However, it is not known if co-administration of antimalarial drug with rutin will reverse the apoptotic effects of malarial infection. Plasmodium berghei-infected mice were assigned into groups as follows: groups I to III were treated with the vehicle (Parasitised Untreated, PU), 10 mg/kg body weight of Artesunate-Mefloquine (AM) and Dihydroartemisinin-Piperaquine (DP) respectively. Groups IV to VII were treated with AM, DP but co-administered with 100, 200 mg rutin/kg body weight while groups VIII and IX received rutin (100 and 200 mg/kg body weight). Liver mitochondrial Permeability Transition (mPT) and ATPase (mATPase) were determined spectrophotometrically. Caspases 3 and 9 were assayed using ELISA while the levels of bax, cytochrome c release (CCR), p53 and bcl-2 expressions were assayed immunohistochemically. The mPT pore opening fold of 5 (PU), 16 (AM), 14 (AM + 100 mg rutin/kg body weight), 9 (AM + 200 mg rutin/kg body weight), 4(DP), were observed relative to calcium (24) while DP, rutin and their combinations did not open the pore. AM and DP significantly increased caspases 3 and 9 activities, enhanced mATPase activity but co-treatment with rutin (100 mg/kg) decreased these effects significantly. AM + rutin (100 mg/kg body weight) significantly decreased bax, p53, CCR and increased bcl-2 expression. The results showed that supplementing malarial treatment with rutin decreased apoptosis suggesting that rutin supplementation can minimise apoptosis in malarial infection. •Malaria causes mitochondrial dysfunction.•Some antimalarial drugs cause cellular damage.•Rutin ameliorates cell death-inducing potentials of some antimalarial drugs.•Rutin enhances erythrocyte membrane stabilisation.