Adverse hematological profiles associated with chlorpromazine antipsychotic treatment in male rats: Preventive and reversal mechanisms of taurine and coenzyme-Q10.

Chlorpromazine (CPZ) is one of the most effective antipsychotic drugs used for managing psychotic related disorders owing to its dopamine receptor blocking action. However, pharmacological investigations against CPZ's cytotoxic effect have remained scarce. Hence, this study investigated the preventive and reversal effects of taurine and coenzyme-Q10 (COQ-10), which are compounds with proven natural antioxidant properties, against CPZ-induced hematological impairments in male rats. In the preventive study, rats received oral saline (10 ml/kg), taurine (150 mg/kg/day), COQ-10 (10 mg/kg/day) or in combination for 56 days, alongside CPZ (30 mg/kg, p.o.) between days 29-56. In the reversal protocol, rats had CPZ repeatedly for 56 days before taurine and COQ-10 treatments or their combination from days 29-56. Rats were also given taurine (150 mg/kg/day), and COQ-10 (10 mg/kg/day) alone for 56 days. Serums were extracted and assayed for hematological, with oxidative and inflammatory markers. CPZ induced decreased red/white blood cells, erythropoietin, platelet count, packed cell volume and hemoglobin, neutrophil, and lymphocyte, which were prevented and reversed by taurine and COQ-10, or their combination. Taurine and COQ-10 improved mean corpuscular volume, hemoglobin concentration, with increased erythropoietin levels relative to CPZ groups. CPZ-induced increased malondialdehyde, tumor necrosis factor-alpha and interleukin-6 levels with decreased interleukin-10, glutathione, and superoxide-dismutase were prevented and reversed by taurine and COQ-10 in comparison with CPZ groups. Taurine and COQ-10 alone notably improved the antioxidant/anti-inflammatory status relative to controls. Among other mechanisms, taurine and COQ-10 abated CPZ-induced hematological deficiencies, via decreased serum levels of oxidative stress, and pro-inflammatory cytokines release, with increased antioxidants and anti-inflammation function.

Prevention and reversal of chlorpromazine induced testicular dysfunction in rats by synergistic testicle-active flavonoids, taurine and coenzyme-10.

Evidences have shown that alterations in testicular dehydrogenase and ionic-ATPase activities have important implications in spermatogenesis and sperm capacitation, a penultimate biochemical change required for fertilization. Previous studies have revealed that taurine and coenzyme-Q10 (COQ-10), which are synergistic testicle-active bioflavonoids, with proven gonadotropin-enhancing properties reduce testicular damage in rats. Hence, this study investigated the effects of taurine and COQ-10 or their combination alone, and in the preventive and reversal of chlorpromazine-induced inhibition of testicular dehydrogenase enzymes, electrogenic pumps, sperm capacitation and acrosomal-reaction in male Wister rats. In the drug-treatment alone or preventive-protocol, rats received oral treatment of saline (10 mL/kg), taurine (150 mg/kg/day), COQ-10 (10 mg/kg/day) or both alone repeatedly for 56 days, or in combination with chlorpromazine (30 mg/kg/p.o./day) from days 29-56. In the reversal-protocol, the animals received chlorpromazine for 56 days prior to saline, taurine, COQ-10 or the combination from days 29-56. Thereafter, spermatogenesis (sperm count, viability, motility and morphology), testicular dehydrogenase [3beta-hydroxysteroid dehydrogenase (3ß-HSD), 17beta-hydroxysteroid dehydrogenase (17ß-HSD), glucose-6-phosphate dehydrogenase (G6PDH), lactate dehydrogenase-X (LDH-X)], ATPase (Na+/K+, Ca2+, Mg2+, H+) activities, sperm capacitation and acrosomal reaction were evaluated. Taurine and COQ-10 or their combination increased spermatogenesis, testicular 3ß-HSD, 17ß-HSD, G6PDH and LDH-X enzymes of naïve and chlorpromazine-treated rats. Both taurine and COQ-10 increased Na+/K+, Ca2+, Mg2+ and H+-ATPase activities. Also, taurine and COQ-10 or their combination prevented and reversed chlorpromazine-induced inhibition of sperm capacitation and acrosomal-reaction. The study showed that taurine and COQ-10 prevent and reverse chlorpromazine-induced inhibition of spermatogenesis, epididymal sperm capacitation and acrosomal reaction in rats through increased testicular dehydrogenases and electrogenic pump activities.

Taurine and coenzyme Q10 synergistically prevent and reverse chlorpromazine-induced psycho-neuroendocrine changes and cataleptic behavior in rats.

Over the years, mounting evidences have suggested a strong association between chronic chlorpromazine therapy, a popular first-generation antipsychotic drug, and psycho-neuroendocrine changes. In this study, we aim to examine whether treatment with taurine and coenzyme Q10 (COQ-10), compounds with steroidogenic-gonadotropin hormone-enhancing properties, can attenuate the negative impacts of chlorpromazine on steroidogenic, gonadotropin, thyroid and HPA-axis hormones, dopamine levels, catalepsy behavior and neuronal cells of the hypothalamus and pituitary gland in the preventive and reversal treatments in male Wister rats. In the drug treatment alone or preventive protocol, rats received oral administration of saline (10 mL/kg), taurine (150 mg/kg/day), COQ-10 (10 mg/kg/day), or both (taurine + COQ-10/day) alone for 56 consecutive days, or in combination with oral chlorpromazine (30 mg/kg/day) treatment from days 29 to 56. In the reversal protocol, the animals received chlorpromazine or saline for 56 days prior to taurine, COQ-10, or the combination from days 29 to 56. Thereafter, serum prolactin, steroidogenic (testosterone, estrogen, progesterone), gonadotropin (luteinizing hormone, LH, follicle-stimulating hormone, FSH), thyroid (thyrotropin-stimulating hormone, tetraiodothyronine, triiodothyronine) hormones, corticosterone, brain dopamine levels and cataleptic behavior were investigated. The histopathological features of the hypothalamus and pituitary gland were also evaluated. Taurine, COQ-10, or their combination prevented and reversed chlorpromazine-induced hyperprolactinemia, decrease in FSH, LH, testosterone, progesterone and dopamine concentrations, as well as the increase in estrogen levels. Taurine and COQ-10 reduced the changes in thyroid hormones, corticosterone release, histological distortions of the hypothalamus and the pituitary gland of chlorpromazine-treated rats. Taurine and COQ-10 attenuated chlorpromazine-induced catalepsy. The study showed that taurine and COQ-10 prevented and reversed chlorpromazine-induced changes in reproductive, thyroid hormones, dopamine level, corticosterone release, neurodegenerations, and cataleptic behavior in rats.