PROTECTIVE EFFECT OF THYMOQUINONE ON THE LIVER TISSUES OF 7, 12-DIMETHYLBENZ (A) ANTHRACENE INDUCED EXPERIMENTAL BREAST CANCER RATS

Objective: Thymoquinone (TQ), the main active ingredient of the volatile oil isolated from the Nigella sativa seeds has been shown to possess a widearray of pharmacological effects. Recently, we have reported the anticancer potential of TQ in 7, 12-dimethylbenz (a) anthracene (DMBA) inducedrats. DMBA acts as a potent site and organ-specific carcinogen by generating various reactive metabolic intermediates leading to oxidative stress. Thepresent study was hypothesized to explore the protective effect of TQ against DMBA induced liver injury in rats.Methods: DMBA was used to induce breast cancer in rats. Oral treatment of TQ (25 mg/kg body weight) to DMBA induced rats daily for 4 weeks wasfound to be effective against DMBA induced mammary gland carcinogenesis in female Wistar rats. The levels of nucleic acids, oxidative stress markand antioxidants were determined. The activities of Phase I and Phase II enzymes, tricarboxylic acid (TCA) cycle enzymes were assayed.Results: The increased levels of DNA and RNA were found to be decreased on treatment with TQ. The altered activities of Phase I and Phase IIbiotransformation enzymes were found to be regulated on treatment with thymoqionone. The hepatoprotective nature of TQ was assessed byanalyzing the markers of oxidative stress, and antioxidant competence in DMBA induced rats. Treatment with TQ revealed a significant decline in thelevels of lipid peroxides, and a significant improvement in the levels of enzymatic and non-enzymatic antioxidants in the liver tissue. In addition, TQmodulated the activities of TCA cycle enzymes.Conclusion: The results of the present study clearly indicate that TQ protects the tissues from oxidative stress-mediated damage which is evidentfrom improved antioxidant status.Keywords: 7, 12-dimethylbenz (a) anthracene, Thymoquinone, Oxidative stress, Liver tissues, Antioxidant potential

ORAL ADMINISTRATION OF THYMOQUINONE ATTENUATES BENZO (A) PYRENE INDUCED LUNG CARCINOGENESIS IN MALE SWISS ALBINO MICE

Objective: The present study has been designed to unravel the anticancer potential of thymoquinone against Benzo(a)pyrene induced lung cancer in male swiss albino mice. Thymoquinone (C10H12O20 )is a bioactive compound derived from the medicinal plant Nigella sativa. Thymoquinone (TQ) has been shown to exert anticancer effect on various cancer cell lines and there is no study on the efficacy of TQ on Benzo(a)pyrene [B(a)P] induced lung carcinogenesis in male swiss albino mice. Methods: The changes in heme indices ( RBC, Hb, WBC, monocytes, lymphocytes and neutrophils), membrane bound ATPases (Na+/K+ ATPase, Mg2+ ATPase and Ca2+ ATPase) in control and experimental animals were analysed in serum and lung tissue homogenate. Results: Lung cancer induced animals showed a considerably altered levels of heme indices with concomitant decreased levels of membrane bound ATPases in the lung tissue and erythrocyte membrane. Oral administration of TQ at a dose of 20mg/kg b.w brought back the levels of the biochemical parameters to near normal. Conclusion: TQ supplementation restored the detrimental effects induced by B (a) P, indicating its anticancer potential in the treatment of experimental lung carcinogenesis

Effects of Thyroxine Replacement on Glycosylated Hemoglobin Levels in Non Diabetic Patients with Overt Hypothyroidism

INTRODUCTION: HbA1c is used for screening as well as for diagnosing Diabetes Mellitus. HbA1c - 4% – 5.7% - normal, 5.7%- 6.5% - pre-diabetes, > 6.5% - diabetes mellitus. It depends on ambient levels of glycemia over the preceeding 2-3 months but also on the RBC turnover from the bone marrow. HbA1c may not accurately reflect the level of glycemia in conditions of altered erythrocyte turnover. Conditions which are associated with a low RBC turnover (hypoproliferative anemias) are associated with a falsely elevated HbA1c. Hypothyroidism being one of the causes of hypoproliferative anemia may lead to false elevation of HbA1c resulting in erroneous diagnosis of pre diabetes or diabetes. AIMS AND OBJECTIVES: 1. The objective of our study was to determine the effects of hypothyroidism on HbA1c levels in individuals without diabetes. 2. To observe whether HbA1c falls in hypothyroid patients following treatment. 3. To assess the validity of using HbA1c for diagnosing diabetes in hypothyroid patients. MATERIAL AND METHODS: The study was conducted on 100 patients who were admitted and attending OP in Govt. Rajaji hospital, Madurai. It was a Prospective study for a duration of 6 Months. The study was conducted on non diabetic overt hypothyroid patients meeting the following criteria. Inclusion Criteria: All patients with Overt Hypothyroidism. Exclusion Criteria: • Diabetes mellitus (FBS > = 126 mg/dl, PPBS: > = 200 mg/dl). • Impaired glucose tolerance (2h post 75g OGTT is between 140- 199 mg/dl). • Hb < 10 g/dl. • Known hemoglobinopathies. • Renal or Liver diseases. • Recent blood transfusions (< 3 months). • Pregnant patients. History from the patient was collected from previously designed proforma with informed consent. Patients were followed up for a period of 6 months to check for FBS, PPBS and HbA1c levels before and after thyroxine replacement. Laboratory investigations includes Complete blood count, Reticulocyte count, Fasting blood glucose, Post prandial blood glucose, HbA1c, TSH/T4, Liver and renal function tests. RESULTS: In our study consisting of 100 patients majority of the patients belong to age group 36-45 (43%). Females were more in number (85%). The baseline TSH values on an average was between (10-20) in 66% of the study population. T4 levels were between 1.1-2.0 in 49% of patients. In these patients the post treatment FBS and PPBS were with normal limits. The HbA1c estimation was done and was found to be increased. The average HbA1c was around 5.83%. This lead to false diagnosis of dysglycemia in 67% of patients. False diagnosis of impaired glucose tolerance -60% and diabetes was 7%. thyroxine replacement and achievement of euthyroidal state, follow up was done for 3 months post achieving euthyroidal state on account of approximately 120 days of life span of RBC. The T4 and T4 on the average was found to be TSH-3.66 and T4- 7.85 within normal range, although there was no difference in fasting and post prandial blood sugars the mean HbA1c decreased to 5.25%. CONCULSION: Its concluded from the above study that HbA1c are falsely elevated out of proportion to the level of glycemia in patients with hypothyroidism which leads to false diagnosis of dysglycemia and it is lowered without any change in blood sugar levels after thyroine replacement and achievement of a euthyroidal state. Therefore in hypothyroid patients diagnosis of pre diabetes or diabetes should only be based on fasting blood glucose and post prandial blood glucose. So we conclude that HbA1c is not a valid test for diagnosis of prediabetes or diabetes in the presence of hypothyroidism

IN SILICO DOCKING STUDIES ON THE ANTI-CANCER EFFECT OF THYMOQUINONE ON INTERACTION WITH PTEN- A REGULATOR OF PI3K/ AKT PATHWAY

Objective: The statistics on cancer imposes the urge to extend new methods to control this deadly form of the disease. Phosphatase and tensinhomolog located on chromosome 10q23 (PTEN) is inactivated in a subset and AKT is frequently activated in cancer. The PTEN is the central negativeregulator of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling cascade that influences multiple cellular functions including cell growth, survival,proliferation and migration in a context-dependent manner. Dysregulation of this signaling pathway contributes to different types of cancers. Theobjective of the study is to explore the anti-cancer potential of thymoquinone (TQ) by analyzing the interaction between TQ with the target proteinPTEN.Methods: The three dimensional structure of TQ is designed using in-silico methods, and the structure of PTEN is obtained from National Center forBiotechnology Information against protein data bank. The query sequence from 8 to 353 amino acids was found to be 85% homologous to ID5R. Forthe target protein PTEN with 403 residues, protein families analysis covered the important domains in PTEN.Result: TQ showed the binding energy of −7.37 Kcal/mol against PTEN with three hydrogen bonds.Conclusion: Present study suggests that TQ might inhibit abnormal cell proliferation occurring in cancer by modulating the activity of PTEN,a negative regulator of PI3K/AKT pathway.Keywords: Cancer, Thymoquinone, Phosphatase and tensin homolog located on chromosome 10q23, Docking and hydrogen bonds.Â

BREAST CANCER: TYPES, EPIDEMIOLOGY &amp; AETIOLOGY -A REVIEW

ABSTRACT Breast carcinoma is the most widespread cancer in women worldwide. Breast cancer is the most common cancer among women and is the second leading cause of cancer related death. According to the American Cancer Society, about 2 49,100 women will be diagnosed with breast cancer and more than 39,840 women are expected to die from breast cancer in 20111. The average women&apos;s lifetime risk of developing breast cancer is approximately 12%. The risk factors involved in the development of breast cancer include: older age, environmental factors, early menarche, late menopause, family history, prolonged hormone replacement therapy and alcohol consumption. A number of genes including BRCA1, BRCA2, HER-2 are also identified as causative agents. Hence this review highlights the types, epidemiology and causes of breast cancer briefly