The interrelationship between
gasotransmitters and oxidative stress,
inflammation and apoptosis in lead-induced hepatotoxicity was investigated in this study. On prolonged exposure, lead was accumulated in liver tissue of rats and impaired liver function and structure as assessed by measurement of the serum hepatic function markers and by histopathological examination. The accumulated
metal induced oxidative stress,
inflammation and apoptosis in the liver. Also, it increased
nitric oxide (NO) production and decreased
hydrogen sulfide (H2S) level and
heme oxygenase (HO-1) concentration in liver tissue. Decreasing of NO production by L-
N(G)-nitroarginine methyl ester (
L-NAME) and increasing of H2S level by
sodium hydrosulfide (
NaHS) and
carbon monoxide (CO) level by
carbon monoxide-releasing molecule-A1 (CORM-A1) inhibited lead-induced impairment of liver function and structure. Concomitantly, these agents inhibited lead intoxication-induced oxidative stress,
inflammation, apoptosis, nitrosative stress and reduction of HO-1 concentration and H2S level. Furthermore, concurrent treatment with these agents inhibited lead intoxication-induced increase in the
protein expressions of inducible
NO synthase,
tumor necrosis factor-alpha,
interleukin-1beta and
caspase-3 as well as decrease in
protein expressions of HO-1 and
cystathionine-γ-
lyase in the liver. NO donor,
l-arginine and H2S and CO biosynthesis inhibitors, trifluoro-DL-
alanine and
zinc deutroporphyrin, respectively aggravated the toxic effects of lead. These results indicate, for the first time, that there is an interrelationship between
gasotransmitters and lead-induced hepatotoxicity. The ability of L-N
AME,
NaHS and
CORM-A1 to provide protective effects against lead-induced hepatotoxicity may positively correlate, to their ability to suppress hepatic oxidative stress, nitrosative stress,
inflammation and apoptosis.