Modification of inherent and drug-induced dopaminergic activity after exposure to benzo(α)pyrene

Neurotoxicity may be an overlooked consequence of benzo[a]pyrene exposure that is relevant to human health risk assessment

“…The exposure of male Wistar rats to 50 mg BaP/kg-bw-day for 3 days by intraperitoneal injection led to a 4-fold increase in DA in the hippocampus, no change in the hypothalamus, and a 25% reduction in DA levels in the caudate putamen [56]. Comparison of the effects of BaP treatment on basal and pharmacologically-mediated neurotransmitter levels suggests that BaP may act preferentially on brain areas with greater dopaminergic innervation [56]. It has been hypothesised that BaP may exert its neuromodulatory actions through activation of the genes coding for the CYP1A family and DA metabolism enzymes [56].…”

“…injection 1 4 Elevated level of pro-inflammatory cytokines, activation of microglia and astrogliosis in brain Rat, Wistar <, 3 mo [56] Intraperit. injection 10 3 Altered dopaminergic activity in several brain regions, increased dopamine (DA) levels (hippocampus) and DA turnover (caudate putamen) Rat, F-344 <, 8 weeks [11] Oral gavage 25 1 Impaired motor activity.…”

“…Additional studies are required to establish conclusively whether these differences are species-or sex-specific. The exposure of male Wistar rats to 50 mg BaP/kg-bw-day for 3 days by intraperitoneal injection led to a 4-fold increase in DA in the hippocampus, no change in the hypothalamus, and a 25% reduction in DA levels in the caudate putamen [56]. Comparison of the effects of BaP treatment on basal and pharmacologically-mediated neurotransmitter levels suggests that BaP may act preferentially on brain areas with greater dopaminergic innervation [56].…”

“…Comparison of the effects of BaP treatment on basal and pharmacologically-mediated neurotransmitter levels suggests that BaP may act preferentially on brain areas with greater dopaminergic innervation [56]. It has been hypothesised that BaP may exert its neuromodulatory actions through activation of the genes coding for the CYP1A family and DA metabolism enzymes [56].…”

Biological Membranes Are Nanostructures that Require Internal Heat and Imaginary Temperature as New, Unique Physiological Parameters Related to Biological Catalysts

“…In particular, these isoforms of CYP are involved in the biotransformation of important pre-carcinogens present in the environment, such as barbital drugs, anticancer drugs, and polycyclic aromatic hydrocarbons (PAH). The PAH benzo(a)pyrene (B(a)P) is an important toxin that functions as an inducer of CYP1A(1/2), among other genes, and B(a)P is a pre-carcinogenic substrate for some enzymes [17]. Among the many chemical transformations catalyzed by CYP enzymes, steroid hormone hydroxylation and cleavage are of particular interest because of their mechanistic complexities and essential roles in physiology.…”