Hydrogen sulfide may attenuate methylmercury-induced neurotoxicity via mitochondrial preservation

- NaHS reduced MeHg-induced oxidative stress.
- NaHS attenuated MeHg-induced mitochondrial damage.
- NaHS decreased the number of MeHg-induced apoptotic cells.
- NaHS increased DNA, RNA, acetylcholinesterase activity and Na+/K+-ATPase activity.

Hydrogen sulfide (H2S) is a protective molecule and a novel gaseous mediator. Here we explored whether H2S donor (NaHS) could attenuate methylmercury (MeHg)-induced neurotoxicity in rats. The adult rats were randomly divided into four groups, i.e., control, NaHS, MeHg, and NaHS + MeHg groups. Rats of the NaHS + MeHg group were intraperitoneally (i.p) injected with 5.6 mg/kg/d of NaHS together with 5 μg/kg/d of MeHg. Rats of the MeHg group and NaHS group were injected with 5 μg/kg/d of MeHg and 5.6 mg/kg/d of NaHS, respectively. All treatments were continued for 20 d, and the cerebral cortex of the rats was evaluated. The results showed that NaHS significantly reduced MeHg-induced oxidative stress, as indicated by reduced lipid peroxide content, and increased glutathione levels and glutathione peroxidase and thioredoxin reductase activities. NaHS attenuated MeHg-induced mitochondrial damage, as indicated by increased mitochondrial activity, reduced mitochondrial swelling, and the release of cytochrome C and apoptosis-inducing factors. NaHS also decreased the number of apoptotic cells compared to that observed in MeHg only-treated rats, as indicated in a TUNEL assay. Finally, NaHS increased DNA and RNA content, and the activities of acetylcholinesterase and Na+/K+-ATPase. These indices were all lower in the MeHg group than in the control group, and NaHS alone did not observably influence any of these indices compared to the control. Our results demonstrate that H2S may protect against MeHg-induced neurotoxicity, and the mechanisms appear to involve the inhibition of oxidative stress and the protection of mitochondria.