Inhibition of inducible nitric oxide synthase in murine visceral larva migrans: effects on lung and liver damage.
The roles of nitric oxide production and oxidative process were studied in mice infected with Toxocara canis and treated with aminoguanidine which is a specific inhibitor of inducible nitric oxide synthase (iNOS). Relations of nitric oxide synthase inhibition and tissue pathology were assessed by biochemical, histological and immunohistochemical methods. In experiments, Balb/c albino mice were inoculated with T. canis eggs either with or without aminoguanidine treatment or alone, at 24th, 48th hours and on 7th days. LPx and SOD values in liver tissue and plasma were measured. Liver and lung tissues were evaluated for the pathological lesions. The expression of eNOS and iNOS in both tissues were studied with immunohistochemistry in the same intervals. We observed significant differences between T. canis infected and aminoguanidine treated animals. Larval toxocarosis led to oxidative stress elevation in plasma. Microscopic examination of the liver histological sections revealed pathological lesions in the hepatic parenchyma in infected mice. In the mice received T. canis eggs plus aminoguanidine, the sinusoidal areas were enlarged. Histological lesions were more severe at 48 hours after infection. Numbers of eNOS and iNOS expressing epithelial cells were increased in the T. canis infected mice. The activities of eNOS and iNOS were also observed in the body of the larvae which have migrated to lung and liver. As a result, we have demonstrated that in vivo production of eNO and iNO during T. canis infection cause direct host damages and it is strongly related to the oxidative stress. We propose that larval NO can also be effective in larval migration, but it needs further investigation on distribution of NO in larvae.
Demirci
Cihan
C
Department of Biology, Faculty of Science, Istanbul University, 34459, Vezneciler, Istanbul, Turkey. cihan@istanbul.edu.tr
Gargili
Aysen
A
Kandil
Aslt
A
Cetinkaya
Handan
H
Uyaner
Ilhan
I
Boynuegri
Basak
B
Gumustas
M Koray
MK
D000818:Animals; D004285:Dogs; D004790:Enzyme Induction; D005260:Female; D007814:Larva / Q000502:physiology; D007816:Larva Migrans, Visceral / Q000201:enzymology* / Q000473:pathology; D008099:Liver / Q000473:pathology*; D008168:Lung / Q000473:pathology*; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D017166:Toxocara canis / Q000502:physiology*
D052247:Nitric Oxide Synthase Type II