Biologia 66/1: 187—193, 2011 Section Zoology DOI: 10.2478/s11756-010-0136-1 Effect of maternal exposure of fluoride on oxidative stress markers and amelioration by selected antioxidants in developing central nervous system of rats Piler Mahaboob Basha & Narayanaswamy Madhusudhan Department of Zoology, Bangalore University, Bangalore-560 056, India; e-mail: pmbashabub@rediffmail.com Abstract: Fluoride has been implicated as a pathologic mediator of fluorosis. Interestingly neuronal destruction, synaptic injury occurs by a mechanism involving oxidative stress, however, its effects in developmental stages of life, during maternal fluoride exposure and amelioration are not elucidated. In the present study, pregnant Wistar albino rats were exposed to 50 and 150 ppm fluoride in drinking water during gestation and post gestation. After parturition the pups born to the experimental animals were administered daily with selected antioxidants for 21 consecutive days. Fluoride administration substantially enhanced fluoride accumulation, lipid peroxidation and decreased the activity of superoxide dismutase, cata- lase, glutathione peroxidase, glutathione-S-transferase and glutathione levels in discrete regions of central nervous system. The results significantly (P < 0.05) demonstrated the effect of fluoride through exacerbated oxidative damage and disrupted antioxidant homeostasis, leading to altered neuronal integrity. The administration of antioxidants vitamin E, vitamin C, se- lenium and zinc produced a promising accost and timely intervention to the aggravated impairment during highly vulnerable early stage of life. Key words: antioxidants; fluoride toxicity; fluorosis; lipid peroxidation; oxidative stress Introduction Chronic fluorosis is prevalent in many parts of the world, caused by excessive ingestion of fluoride over prolonged period and endangers the health of humans and animals (Zhan et al. 2005). High exposure to flu- oride may occur from natural (drinking water, vegeta- bles and fruits from endemic areas) and industrial (flu- orine emission) sources and/or from the misuse of flu- oride containing dental care products or drugs (Borke & Whitford 1999; Ozsvath 2009). The WHO guideline value for fluoride is 1.5 ppm and concentrations beyond this value carry an increased risk of dental/skeletal and/or soft tissue fluorosis. Following ingestion, fluo- ride accumulates in bones and teeth, disperses towards cardiac muscle, liver, brain, kidney and other soft tis- sues (Shivashankara et al. 2000; Vani & Reddy 2000) and cause metabolic disturbances (Chirumari & Reddy 2007). In vivo studies confirm that the fluoride ion is strongly reactive due to its high negative charge den- sity and alter the distribution of electrons, including enzymes and membrane transport proteins, thereby af- fecting the metabolites of many cells, tissues and organs (Korkmaz 2000). In advanced stages of fluorosis, neu- rological manifestations such as paralysis of limbs, ver- tigo, spasticity in extremities and impaired mental acu- ity are observed in humans (Inkielewicz & Czanowski 2008; Inkielewicz & Krechniak 2004; Mullenix et al. 1995). As seen in many chronic degenerative diseases, in- creased production of reactive oxygen species (ROS) and lipid peroxidation has been considered in pathogen- esis and recent studies suggest that oxidative stress is a possible pathologic mediating factor in fluoride toxic- ity (Birkner et al. 2006; Inkielewicz & Czanowski 2008; Krechniak & Inkielewicz 2005), but its occurrence in the developing stages of life during maternal fluoride exposure is unclear. Exposure to chemical agents dur- ing early developmental stages of life results in long- term irreversible consequences with their structure and function and account for qualitative differences in age- related susceptibility (Fu & Ji 2003; Plantin et al. 1987). Preponderance of studies suggests that uptake, ac- cumulation, and toxicity of many xenobiotics can be modified by dietary factors (Halliwell 2001; Zheng et al. 2003) and similarly the use of antioxidants and antioxidant-rich foods are indicated for the manage- ment of fluorosis (Chinoy & Shah 2004; Susheela & Bhatnagar 2002). Thus the present study was aimed to assess the toxic effects of fluoride in developing cen- tral nervous system (CNS) of rats and to determine the protective role of antioxidants supplemented. Material and methods Animals Laboratory bred premated albino rats Rattus norvegicus, Wistar strain obtained from Sri Raghavendra enterprises, c 2011 Institute of Zoology, Slovak Academy of Sciences