Omega-3 fatty acid attenuates oxidative stress in cerebral cortex, cerebellum, and hippocampus tissue and improves neurobehavioral activity in chronic lead-induced neurotoxicity.

Objectives: In view of the increasing risk of lead on human health, the present study has been carried out to investigate the neuroprotective effect of omega-3 fatty acid on chronic lead-induced neurotoxicity and behavioral impairment in rats. Methods: Different neurobehavioral parameters, biochemical assays, and histopathological analyses in brain regions of rats were conducted. Results: Rats exposed to different doses of lead (lead acetate 2.5, 5.0, 7.5 mg/kg body weight p.o. for 90 days) caused a significant decrease in body weight, brain weight, and behavioral changes as compared to controls. Abnormal histopathological and increased levels of lead in blood and brain regions increased the levels of ROS, LPO, PCC and decreased the levels of GSH with concomitant reduction in SOD, CAT, and GPx activities in the brain region of rats treated with different doses of lead as compared to controls. Co-treatment of lead with omega-3 fatty acid (500 mg/kg body weight p.o. for 90 days) decreased the levels of ROS, LPO, PCC, and increased the level of GSH, also increased SOD, CAT, and GPx activity and showed improvements in behavioral as well as histopathological changes as compared to lead-treated groups. Discussion: Our results proved that omega-3 fatty acid improved behavioral deficits, altered histopathological and oxidative stress in lead-intoxicated rats. Among three different doses, 2.5 mg/kg b.wt. of lead along with omega-3 fatty acid was the most preventive dose for the neurotoxicity. This work reveals the potential of omega-fatty acid as a protective drug for lead neurotoxicity.

Attenuation of Lead-Induced Neurotoxicity by Omega-3 Fatty Acid in Rats.

BACKGROUND: Lead is widely distributed in the environment and has been found to be associated with various health problems including neurodegenerative diseases. PURPOSE: In view of the increasing health risk caused by lead, this study has been carried out to investigate the neuroprotective effect of omega-3 fatty acid (omega-3FA) in lead-induced neurotoxicity in rats. METHODS: Biochemical parameters including oxidative stress in brain regions, lead levels in blood and brain regions and histopathological examination of brain regions of rats were carried out in the present study. RESULTS: Rats exposed to lead (lead acetate 7.5 mg/kg body weight p.o. for 14 days) caused a significant increase in the levels of lipid peroxidation, protein carbonyl content, ROS production and decreased the activities of glutathione peroxidase, superoxide dismutase and catalase in the cerebellum and cerebral cortex, respectively, as compared to controls. Abnormal histopathological changes and increase in the levels of lead in blood and brain were also observed as compared to controls. Co-treatment of lead with omega-3FA (750 mg/kg body weight p.o. for 14 days) decreased the levels of lipid peroxidation, protein carbonyl content, ROS production and increased the activities of glutathione peroxidase, superoxide dismutase and catalase and showed protection in the histopathological study as compared to rats treated with lead alone. CONCLUSIONS: The result of the present study shows that lead-induced oxidative stress and histopathological alteration in the brain region were significantly protected with co-treatment of lead and omega-3FA. This could be due to its strong antioxidant potential and metal-binding property.

Immunohistochemical expression of MIB-1 and PCNA in precancerous and cancerous lesions of uterine cervix.

BACKGROUND AND OBJECTIVE: The present study was done to analyze the immunoexpression of diagnostic markers (MIB-1: molecular immunology borstel and PCNA: proliferating cell nuclear antigen) in grading cervical intraepithelial lesion (CIN) and squamous cell carcinoma (SCC) in cervix. SETTING AND DESIGN: Total 150 cervical biopsies were divided into four groups respectively; Group I-Normal (n = 32), Group II- CIN (n = 60), Group III- SCC (n = 44), Group IV- CA cervix (n = 14) respectively. MATERIALS AND METHODS: These biopsies were stained with monoclonal antibodies by streptavidin--biotin method. Mean labeling index was calculated and grading was performed using the I--III scoring system. STATISTICAL ANALYSIS: Findings were correlated with age and menopausal status. Statistical analysis was done by using student sample't' test and analysis of variance (ANOVA) by SPSS 10 package. RESULTS: MIB-1 immunostaining was positive in 112/150 (74.6%) cases and PCNA in 118 /150 (78.6%) cases. Labeling indices showed linear progression from normal to CIN to SCC to cancer lesion. Few cases of low-grade CIN lesion had high proliferative index. A significant positive correlation was found between age and PCNA and MIB-1 values (P < 0.05) when comparison was made for all the cases. CONCLUSION: These markers may be useful in identifying low-grade CIN lesion with high proliferative index. These cases should be kept for follow up studies so that proper intervention can be taken at an early stage. This method is simple and cost effective and can easily be done in formaline-fixed paraffin embedded tissues in a clinical laboratory for grading CIN and SCC lesions in cervix.

MIB-1 and PCNA immunostaining as a diagnostic adjunct to cervical Pap smear.

The present study was done to determine the role of MIB-1 (Molecular Immunology Borstel) and proliferating cell nuclear antigen (PCNA) proliferative index as a diagnostic adjunct to cervical Papanicolaou (Pap) smear for the identification of ascending grades of cervical intraepithelial neoplasia (CIN) developing into cancer in the human uterine cervix. A total of 49 adequate Pap smears with consensus diagnosis were destained for immunocytochemical staining (MIB-1 and PC10). Staining was done by streptavidin-biotin method after antigen retrieval. MIB-1 and PC10 labeling index (LI) were calculated in each case and divided into three groups, i.e., <10%, 10-20%, and >20%, respectively. Statistical analysis was done by using the SPSS 10.0 package. The comparisons were made using analysis of variance (ANOVA) and independent sample t-test. Bivariate and Pearson's correlation coefficient were used to obtain correlations between different groups. Out of 49 cases, 40 cases (81.6%) showed positive immunostaining with MIB-1 and PCNA. Proliferative LI of MIB-1 and PCNA increased with the ascending grades of CIN lesions to carcinoma. The highest proliferative index (mean +/- SD) for PCNA and MIB-1 were observed for the carcinoma group (PCNA LI, 39.200 +/- 1.6865; MIB-1LI, 35.300 +/- 1.8886). A significant positive correlation between ascending grades of squamous intraepithelial lesion (SIL) and labeling indices of markers (r = 0.87 for MIB-1 and r = 0.88 for PCNA) suggests that MIB-1/PCNA proliferative markers can be used as an adjunct to cytomorphological interpretation of conventional cervical Pap smear.

Ki-67 and AgNOR proliferative markers as diagnostic adjuncts to fine needle aspiration cytology of thyroid follicular lesions.

OBJECTIVE: To differentiate hyperplastic nodules (HPN), follicular adenoma (FA) and follicular carcinoma (FCA) of the thyroid by cytomorphologic features combined with argyrophilic nucleolar organizer regions (AgNORs) and Ki-67 proliferative markers on fine needle aspiration cytology. STUDY DESIGN: Cytomorphologic patterns, along with two proliferation markers, Ki-67 and AgNORs, in fine needle aspirates of 123 histologically confirmed cases of thyroid follicular lesions, including 39 hyperplastic nodules, 70 follicular adenomas and 14 cases of follicular carcinomas, were recorded. RESULTS: Mean AgNOR (mAgNOR) counts and Ki-67 labelling index (LI) were consistently higher in FCA in comparison to FA and HPN irrespective of the cytologic patterns in fine needle aspiration smears. Between benign and malignant lesions, an overlap of 1.83% at the cutoff point of 4.0 was observed in cases of mAgNORs, whereas it was 11.09% at a cutoff of 5.0 in cases of Ki-67 LI. CONCLUSION: mAgNOR counting in fine needle aspiration smears is more sensitive, simple and cost effective as compared to Ki-67 LI for differentiating between benign and malignant thyroid follicular neoplasms.