Lipoic acid inhibits the pulmonary fibrosis of rat induced in acute paraquat poisoning

Objective To explore possible protection mechanisms of α-LA on PQ-induced pulmonary fibrosis.Methods 144 healthy male Sprage-Dawley rats(2 weeks,body weights ranging between 200 and 260 g),randomly divided into two groups:normal control group(A group,n=24)and experimental group(n=120).Experimental group(50 mg/kg,intragastric administration)was administered to all rats of paraquat.Group A was given to equal dose of saline.Then experimental group can be divided into 5 groups based on the different methods of intervention:the B group(n=24,equal dose of saline,peritoneal injection),the C group(n=24,high doses LA,100 mg·kg-1·d-1,peritoneal injection),the D group(n=24,moderate lipoic acid,60 mg·kg-1·d-1,peritoneal injection),the E group(n=24,small lipoic acid,30 mg·kg-1·d-1,peritoneal injection)and the F group(n=24,glutathione,200 mg·kg-1·d-1,peritoneal injection).At the commencement of the experiment,arterial blood was taken about 3 ml to determine NF-κB,and the levels of NO,NOS,TGF-β1 were tested,which were measured at 1th,7th,14th and 28th day after PQ poisoned.Results(1)The levels of NO,NOS,NF-κB had reached peak at 7th day.It was falling in 14th and 28th day little by little,but it was still higher than normal control group,one of the most significant increase in the PQ group.PQ group compared with each intervention groups at 1th,7th,14th and 28th each checkpoint,PQ group manifested significant difference(P0.01);Compared GSH group and each dose LA group,LA big dose group of each checkpoint all significant difference(P0.05),LA medium and small dose group had contributed to differences not obvious.(2)The level of TGF-β1 had peak at 14th day,it started to fall later,but it was still higher than normal control group,one of the most significant increase PQ.Compared with each LA groups and GSH group at each checkpoint,PQ group manifested significant deviation(P0.01);compared with GSH group,big dose LA group showed up significant difference(P0.01),in LA dose group of 7th,14th,in 28th day showed significant difference(P0.05);the level of TGF-β1 in the small dose LA group had significant difference at the 28th day,other than the others checkpoints(P0.05).Conclusions The results showed that PQ-induced pulmonary fibrosis can be alleviated by LA;the mechanism is possible related to its unique antioxidation.On one hand,LA can reduce NF-κB activity and scavenge oxygen free radicals by NF-κB-NOS-NO signal pathway to inhibit oxidative stress;on the other hand,it can inhibit the expression of TGF-β1,and to alleviate lung tissues fibrosis.LA shows the characteristics of fat-soluble and water-soluble,it is not only scavenging oxygen free radicals in cell membrane,but also removes the free radicals of mitochondrial origin.Thereby,LA can protect the lung tissues against lung fibrosis.