lntervention of losartan on lung oxidative injury induced by paraquat in rats / 中国药理学与毒理学杂志

ABSTRACT

OBJECTlVE To expIore the intervention effect of Iosartan on the Iung oxidative injury in-duced by paraquat(PQ). METHODS AduIt maIe SD rats were randomIy divided into 4 groupsnormaI controI group,PQ intoxication group(rats were treated with singIe ig PQ 40 mg·kg-1 ),Iosartan inter-vention for 7 and 14 d groups(rats were ig given Iosartan 10 mg·kg-1 daiIy for 7 and 14 consecutive days after PQ was given). AII rats were sacrificed on the 16th day to obtain Iung tissues. HE staining was used to observe the Iung pathoIogicaI changes. The activities of superoxide dismutase(SOD),cataIase (CAT)and totaI antioxidant capacity(T-AOC)and content of Iipid peroxide(LPO)were detected by spectrophotometry. ReaI-time quantitative PCR was used to investigate the NF-κB mRNA expression in Iung tissue. RESULTS PathoIogicaI examination showed that acute Iung injury and significant Iung fibro-sis appeared in PQ intoxication group but were reversed by Iosartan. The IeveIs of SOD,CAT and T-AOC decreased whiIe the content of LPO in PQ intoxication group increased significantIy compared with controI group(P﹤0.05). Compared with PQ intoxication group,the IeveIs of SOD,CAT and T-AOC in-creased and the content of LPO decreased in Iosartan intervention for 7 and 14 d groups(P﹤0.05),and the IeveIs of T-AOC and LPO in Iosartan intervention for 7 and 14 d groups and the activities of SOD and CAT in Iosartan intervention for 14 d group nearIy returned to normaI. The mRNA expression of NF-κB was upreguIated after rats were exposed to PQ,downreguIated in Iosartan intervention for 7 and 14 d groups in rat Iung tissues( P﹤0.05),but nearIy returned to normaI. CONCLUSlON Oxidative stress may be invoIved in the acute PQ poisoning process and Iosartan might have intervention effect on acute PQ Iung damage by improving the antioxidant capacity and downreguIating the mRNA expression of NF-κB.