Bromobenzene-induced lethal toxicity in mouse is prevented by pretreatment with zinc sulfate.
In the current study, we evaluated the protective effect of zinc (Zn) against bromobenzene (BB) -induced lethal toxicity. We used Zn because this element is known to be an inducer of metallothionein (MT), which is in turn known to serve as an endogenous scavenger of free radicals. We administered Zn (as ZnSO4) at 50 mg/kg subcutaneously once-daily for 3 successive days prior to a single intraperitoneal administration of 1.2 g/kg BB in male ddY mice. Our results showed that pretreatment with Zn completely abolished the BB-induced mortality of mice until 48 h. We also found that pretreatment of mice with Zn significantly decreased the functional marker levels and reduced the histological damage both in liver and kidney as assessed at 18 h post-BB. We also showed that pretreatment with Zn enhanced antioxidative activity, resulting in decreased lipid peroxidation in both liver and kidney. Moreover, BB-induced calcium levels were downregulated by pretreatment with Zn. In addition, Zn-induced MT was decreased in Zn + BB-treated animals, implying that MT was consumed by BB-induced radicals. These findings suggest that prophylaxis with Zn protects mice from BB-induced lethal toxicity by decreasing oxidative stress in liver and kidney, presumably by induction of MT, which scavenges radicals induced by BB exposure.
College of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyamaku, Nagoya, Aichi, 463-8521, Japan; Faculty of Nutrition, Kobe Gakuin University, 518 Arise, Ikawadani-cho, Nishi-ku, Kobe, Hyogo, 651-2180, Japan. Electronic address: h-yoshioka@kinjo-u.ac.jp.
Hiroki
H
Yoshioka
College of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyamaku, Nagoya, Aichi, 463-8521, Japan.
Shiori
S
Fukaya
College of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyamaku, Nagoya, Aichi, 463-8521, Japan.
Nobuyuki
N
Fukuishi
College of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyamaku, Nagoya, Aichi, 463-8521, Japan.
Akito
A
Nagatsu
College of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyamaku, Nagoya, Aichi, 463-8521, Japan.
Tsunemasa
T
Nonogaki
Faculty of Nutrition, Kobe Gakuin University, 518 Arise, Ikawadani-cho, Nishi-ku, Kobe, Hyogo, 651-2180, Japan.
Satomi
S
Onosaka
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000032:analysis; D001219:Aspartate Aminotransferases / Q000097:blood; D001969:Bromobenzenes / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D020011:Protective Agents / Q000494:pharmacology*; D019287:Zinc Sulfate / Q000494:pharmacology*
D000975:Antioxidants; D001969:Bromobenzenes; D020011:Protective Agents; D008315:Malondialdehyde; D019287:Zinc Sulfate; C032036:bromobenzene; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002118:Calcium
Bromobenzene; Kidney; Liver; Metallothionein; Oxidative stress