Hydrogen sulfide attenuates NMDA-induced neuronal injury via its anti-oxidative activity in the rat retina.
Although hydrogen sulfide (H2S) is generally thought to be a toxic gas, it has been reported to protect various tissues against ischemia-reperfusion injury. In the present study, we histologically investigated whether H2S, using sodium hydrosulfide (NaHS) as its donor, had a protective effect on N-methyl-d-aspartate (NMDA)-induced retinal injury in the rat in vivo. Under ketamine/xylazine anesthesia, male Sprague-Dawley rats were subjected to intravitreal NMDA injection. NaHS (0.163-120 μmol/kg) was intraperitoneally administered 15 min before NMDA injection. Morphometric evaluation at 7 days after NMDA injection showed that intravitreal NMDA injection resulted in ganglion cell loss. NaHS dose-dependently prevented this damage. NaHS (120 μmol/kg) significantly decreased the numbers of TUNEL-positive, 4-hydroxy-2-nonenal-positive, and 8-OHdG-positive cells 12 h after NMDA injection. In another experimental series, we demonstrated that NaHS (120 μmol/kg) significantly reduced the retinal injury induced by intravitreal NOC12 (400 nmol/eye), which was a nitric oxide donor and reported to induce oxidative stress, in the retina, 7 days after intravitreal injection. These results suggested that H2S protects retinal neurons against the injury induced by intravitreal NMDA in rats in vivo. Anti-oxidative activity of H2S are possibly involved in underlying protective mechanisms.
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 9-1 Shirokane 5-chome, Minato-ku, Tokyo 108-8641, Japan. Electronic address: sakamotok@pharm.kitasato-u.ac.jp.
Kenji
K
Sakamoto
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 9-1 Shirokane 5-chome, Minato-ku, Tokyo 108-8641, Japan.
Yuka
Y
Suzuki
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 9-1 Shirokane 5-chome, Minato-ku, Tokyo 108-8641, Japan.
Yuki
Y
Kurauchi
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 9-1 Shirokane 5-chome, Minato-ku, Tokyo 108-8641, Japan.
Asami
A
Mori
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 9-1 Shirokane 5-chome, Minato-ku, Tokyo 108-8641, Japan.
Tsutomu
T
Nakahara
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 9-1 Shirokane 5-chome, Minato-ku, Tokyo 108-8641, Japan.
Kunio
K
Ishii
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D058449:Intravitreal Injections; D008297:Male; D016202:N-Methylaspartate / Q000633:toxicity*; D020030:Nitric Oxide Donors; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012162:Retinal Degeneration / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013440:Sulfides / Q000494:pharmacology
D000447:Aldehydes; D000975:Antioxidants; D018690:Excitatory Amino Acid Agonists; D020030:Nitric Oxide Donors; D013440:Sulfides; D016202:N-Methylaspartate; D000080242:8-Hydroxy-2'-Deoxyguanosine; C025451:sodium bisulfide; D003849:Deoxyguanosine; C027576:4-hydroxy-2-nonenal; D006862:Hydrogen Sulfide
N-methyl-D-aspartic acid; hydrogen sulfide; oxidative stress; retina