A Comprehensive Review on Oxysterols and Related Diseases.

The present review aims to provide a complete and comprehensive summary of current literature relevant to oxysterols and related diseases. Oxidation of cholesterol leads to the formation of a large number of oxidized products, generally known as oxysterols. They are intermediates in the biosynthesis of bile acids, steroid hormones, and 1,25- dihydroxyvitamin D3. Although oxysterols are considered as metabolic intermediates, there is a growing body of evidence that many of them are bioactive, and their absence or excess may be part of the cause of a disease phenotype. These compounds derive from either enzymatic or non-enzymatic oxidation of cholesterol. This study provides comprehensive information about the structures, formation, and types of oxysterols even when involved in certain disease states, focusing on their effects on metabolism and linkages with these diseases. The role of specific oxysterols as mediators in various disorders, such as degenerative (age-related) and cancer-related disorders, has now become clearer. Oxysterol levels may be employed as suitable markers for the diagnosis of specific diseases or in predicting the incidence rate of diseases, such as diabetes mellitus, Alzheimer's disease, multiple sclerosis, osteoporosis, lung cancer, breast cancer, and infertility. However, further investigations may be required to confirm these mentioned possibilities.

Effects of treatment with haloperidol and clozapine on the plasma concentrations of thyroid hormones in rats.

OBJECTIVES: Psychoactive drugs are group of compounds used to treat severe mental problems, including psychosis, as well as other conditions. This study assessed clinically relevant side effects of haloperidol and clozapine on the thyroid hormones. METHODS: Haloperidol (0.05 and 2 mg/kg) or clozapine (0.5 and 20 mg/kg) was intraperitoneally injected to male Wistar rats for 28 days. The control group received 2 ml of physiological saline. A chemiluminescent immunoassay was used to measure the plasma levels of thyroid hormones. RESULTS: Plasma concentrations of thyroxine (T4) in rats treated with high-dose (2 mg/kg) of haloperidol decreased significantly compared to the control group (p=0.001). However, both low (0.5 mg/kg) and high clozapine (20 mg/kg) doses did not have a significant effect on the plasma concentrations of T4 and triiodothyronine (T3) (p>0.05). Neither of the compound had a significant effect on T3 plasma concentration levels (p>0.05). CONCLUSIONS: Haloperidol and clozapine act via different mechanisms and may have dissociable effects on thyroid hormones. Following treatment with haloperidol, significant changes in T4, but not in T3, serum levels were observed. Haloperidol and clozapine had different effects on the thyroid hormone levels. These results indicate that antipsychotic treatment can contribute to the thyroid dysfunction. Therefore, greater caution should be applied to the antipsychotics use. The thyroid function of the patients should be closely monitored, while using these drugs.

Effects of clozapine and haloperidol treatment on plasma concentrations of androgen hormones and androgendependent organ changes in rats.

OBJECTIVES: Metabolic and endocrine adverse effects are among the most concerning unfavorable consequences of commonly used psychotropic drugs. The present research was planned to assess and determine the effects of haloperidol and clozapine on testosterone, cortisol, and corticosterone levels and also their influence on androgen-dependent organs in adult male Wistar rats. MATERIALS AND METHODS: Animals were casually distributed into three groups (n = 10 in each group). Drugs were administered intraperitoneally for 28 days. The control group received 2 mL of physiological saline, the second group received haloperidol (0.5 mg/kg), and the third group received clozapine (0.5 mg/kg). The subsequent testosterone, cortisol, and corticosterone plasma concentration levels were analyzed with chemiluminescent immunoassay. RESULTS: Clozapine and haloperidol treatments altered testosterone hormone levels. Testosterone mean values in both the clozapine (1.00-0.58) and haloperidol (0.65-0.62) groups were found to be lower than compared to controls (P = 0.003, P < 0.001). Histomorphometric analysis results also showed reduced testes size and reduced weight of androgen-dependent organs in drug-treated rats. CONCLUSION: It can be suggested that clozapine and haloperidol are effective in reducing the testosterone plasma concentration level and androgen-dependent organ sizes; therefore, clinicians should be aware of these effects when considering the use of antipsychotic drugs.