Aluminum-induced maternal and developmental toxicity and oxidative stress in rat brain: response to combined administration of Tiron and glutathione.
The current study was performed to assess the potential of 4,5-dihydroxy 1,3-benzene disulfonic acid di sodium salt (Tiron) and glutathione (GSH) either individually or in combination against aluminum (Al)-induced developmental toxicity in fetuses and sucklings of Wistar rats. Female rats were exposed to aluminum chloride at a dose of 345 mg/(kg day) oral from days 0 to 16 of gestation and 0 to 16 of post-partum (P.P.). Tiron and GSH were administered at a dose of 471 mg/(kg day) i.p. and 100 mg/(kg day) oral, respectively, on days 5, 7, 9, 11, 13, 15 and 17 of gestation and post-partum. Al caused reduction in number of corpora lutea, number of implantation sites, placental and fetal weight and stunted growth. Skeletal malformations were also observed in fetuses. Maternal toxicity was demonstrated by reduction in body weight gain. Induction of oxidative stress was also recorded in the brain of mother as well as in fetuses and sucklings after Al exposure. Significant decrease was recorded in reduced glutathione, glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), acetyl cholinesterase (AChE) and increase was observed in TBARS and glutathione-S-transferase (GST) in brain of pregnant mothers, fetuses and sucklings. Most of the above parameters responded positively with individual therapy with Tiron, but more pronounced beneficial effects on the above-described parameters were observed when Tiron was administered in combination with GSH. Inductively coupled plasma-atomic emission spectroscopy (ICP-AES) studies also showed significantly high concentration of Al in suckling's brain and maternal blood, brain, placenta and fetal brain. Treatment with Tiron individually or in combination with glutathione, reduced the accumulation of the Al in almost all the organs studied. It is concluded that chelating agents reduced the Al-induced toxicity and Tiron was more effective in reducing blood Al concentration than glutathione when given individually.
Sharma
Pragya
P
Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, Maharashtra, India.
Mishra
Kaushala Prasad
KP
D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology*; D000014:Abnormalities, Drug-Induced; D017607:Aluminum Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D000833:Animals, Suckling; D001842:Bone and Bones / Q000002:abnormalities*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002374:Catalase / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology*; D004338:Drug Combinations; D010064:Embryo Implantation / Q000187:drug effects; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005317:Fetal Growth Retardation; D020567:Fetal Weight; D005978:Glutathione / Q000494:pharmacology*; D005980:Glutathione Reductase / Q000378:metabolism; D018384:Oxidative Stress; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
D017607:Aluminum Compounds; D002614:Chelating Agents; D004338:Drug Combinations; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D002374:Catalase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione