Pinealectomy and melatonin administration in rats: their effects on pulmonary edema induced by α-naphthylthiourea.

We aimed to observe the possible effects of melatonin (MLT) deprivation (pinealectomy) and exogenous MLT administration on pulmonary edema induced by alpha-naphthylthiourea (ANTU), a toxic chemical agent, in rats. Seventy animals were assigned to seven groups: control, sham pinealectomy (PINX), PINX, ANTU (10 mg/kg intraperitoneal on day 30), ANTU + MLT (10 mg/kg/day i.p. for 30 days), ANTU + PINX, and ANTU + PINX + MLT.In this study, pleural effusion (PE) formation, lung weight/body weight (LW/BW) and PE/BW ratios (fluid accumulation and weight values in the lungs) increase detected. Pre-ANTU MLT administration led to significant decreases in PE, LW/BW, and PE/BW levels. The inhibited glutathione (GSH) and superoxide dismutase (SOD) levels and high malondialdehyde (MDA) levels that ANTU increase lipid peroxidation in the study. MLT administration eliminated oxidative stress by reducing MDA and ameliorating GSH and SOD levels.Pre-ANTU MLT administration led to a significant decrease in interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) levels in the lung when compared to the ANTU group without MLT administration. Post-pinealectomy ANTU administration significantly increased IL-1ß and TNF-α levels when compared to ANTU and MLT administration without pinealectomy. Diffused inflammatory cell infiltration, interstitial pulmonary edema, and histopathological congestion were observed after the administration of ANTU. Severity of the damage was elevated in the ANTU + PINX group. MLT treatment regressed pulmonary effusion and edema and improves lung structure. In brief, the findings suggested that MLT inhibited proinflammatory mediators and could serve as a therapeutic agent to prevent inflammatory disorders.

Anticancer activity of linalool: comparative investigation of ultrastructural changes and apoptosis in breast cancer cells.

Breast cancer is the most common cancer in women in the world. Many anticancer drugs are currently used clinically have been isolated from plant species or are based on such substances. Linalool is aromatic compounds from the monoterpene group. It is the main constituents of essential oils and show antiproliferative, antioxidant, and antiseptic properties. The aim of this study was to investigate the antiproliferativeand apoptotic, effects of linalool in MCF-7 and MDA-MB-231 human breast cancer cells. MCF-7 and MDA-MB-231 human breast cancer cells were treated with different concentrations of linalool (100, 200, 400, 600, 800, 1000 µM) at 24 h and 48 h. MTT assay for cell proliferation and Annexin V assay for apoptosis was done. The morphology of breast cancer cells was investigated by light microscope and scanning electron microscope (SEM). The study show that linalool significantly induced apoptosis in all groups as dose and time-dependent (p < .05). Linalool has apoptotic and antiproliferative properties in a concentration and time-dependent manner in breast cancer cells. The cytotoxic effects of linalool on MCF-7 and MDA-MB-231 human breast cancer cells was found to be associated with apoptotic cell death. Linalool was more effective on MCF-7 human breast cancer cells in smaller amounts.

Linalool exhibits therapeutic and protective effects in a rat model of doxorubicin-induced kidney injury by modulating oxidative stress.

The aim of the present study was to investigate the therapeutic and protective effects of linalool against doxorubicin (DOX)-induced kidney injury. Forty-eight Wistar rats were divided into 8 groups as follows; Control, DOX [20 mg/kg, intraperitoneal (ip) single dose DOX], linalool (LIN50 and LIN100; 50 mg/kg and 100 mg/kg linalool via ip for 5 days, respectively), DOX + LIN50 and DOX + LIN100 (20 mg/kg single dose of DOX via ip on first day and 50 mg/kg and 100 mg/kg linalool via ip, respectively), LIN50 + DOX and LIN100 + DOX (50 mg/kg and 100 mg/kg linalool via ip for 5 days, respectively and 20 mg/kg single dose of DOX via ip on fifth day). Doxorubicin led to a significant increase in the level of malondialdehyde (MDA) in the kidney, whereas superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) levels decreased remarkably when compared with control. On the other hand, LIN supplementation before and after DOX treatment led to a significant decrease in MDA and also increases in SOD, CAT and GSH levels. DOX caused significant increases in the levels of blood urea nitrogen (BUN) and creatinine (Cr) levels in the plasma, while LIN supplementation as a therapeutic and preventive agent led to significant decreases in BUN and Cr levels. The current study demonstrated that LIN supplementation after or before DOX treatment can led to therapeutic and preventive effects against DOX-induced renal damage.

Effects of pinealectomy and crocin treatment on rats with isoproterenol-induced myocardial infarction.

The present study aimed to analyze the effects of pinealectomy and crocin treatment in isoproterenol-induced myocardial damage. Seventy rats were divided into seven groups: control, sham control, pinealectomy (PNX), isoproterenol (ISO; 85 mg/kg on the 29th and 30th days of the experiment, subcutaneous injection), PNX + ISO, PNX + crocin (50 mg/kg/day for 30 days, intragastric administration), and PNX + ISO + crocin. PNX procedure was performed on the first day of the study. A significant increase was observed in serum cardiac damage markers (CK-MB, Troponin I) after ISO administration. ISO administration led to a significant increase in cardiac oxidative stress parameters, such as malondialdehyde (MDA) and total oxidant status (TOS), while it led to a decrease in antioxidant defense system parameters, such as reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and total antioxidant status (TAS) when compared to control groups. Elevated MDA and TOS levels were observed, while reduced SOD and CAT activities, and decreased GSH and TAS levels were observed in the group that underwent PNX and ISO administration when compared to the PNX group. Furthermore, in the PNX + ISO + Crocin group, SOD and CAT activities, and GSH and TAS levels ameliorated and MDA and TOS levels were reduced with the crocin treatment when compared to the PNX + ISO group. Also, marked increases were observed in serum cardiac markers, histopathological and immunohistochemical findings after the crocin treatment. All findings demonstrated that crocin could be employed as a cardioprotective agent due to its antioxidant, anti-inflammatory, and anti-apoptotic properties.

Comparison of ultrastructural changes and the anticarcinogenic effects of thymol and carvacrol on ovarian cancer cells: which is more effective?

Ovarian cancer is the seventh most common cancer worldwide in women. Many anticancer drugs are currently used clinically have been isolated from plant species or are based on such substances. Thymol (5-methyl-2-isopropylphenol) and carvacrol are oxygenated aromatic compounds from the monoterpene group. They are the main constituents of thyme essential oil and show antiproliferative, antioxidant, and antiseptic properties. The aim of this study is to compare the antiproliferative and apoptotic effects of thymol and carvacrol on SKOV-3 ovarian cancer cell line. The cancer cells were treated with different concentrations of thymol and carvacrol (100, 200, 400, 600 µM) at 24 h and 48 h durations. The cell viability was investigated by MTT assay and analysis of apoptosis with annexin V assay was determined. The study show that thymol and carvacrol significantly induced apoptosis in all groups as dose and time-dependent (p < .05). The data in the present study demonstrated that thymol and carvacrol have apoptotic and antiproliferative properties in a concentration-dependent manner toward ovarian cancer cells. SKOV-3 cancer cell line was much more sensitive to the toxic effect of thymol than carvacrol.

Resveratrol reduces light and electron microscopic changes in acetaminophen-induced hepatotoxicity in rats: Role of iNOS expression.

INTRODUCTION: Hepatotoxicity is a major complication of acetaminophen (APAP), a widely used analgesic and antipyretic drug. Resveratrol (RSV) is a naturally occurring diphenol and it has anticancer, antioxidant, and anti-inflammatory properties. OBJECTIVES: In this study, the beneficial effects of RSV on APAP-induced hepatotoxicity was investigated in rats. MATERIALS AND METHODS: Group 1: Ethanol, Group 2: Saline, Group 3: RSV (10 mg/kg/ip), Group 4: APAP (1000 mg/kg/ip/single dose), Group 5: APAP+RSV (20 min after administration of APAP). The rats were sacrificed 24 h after administration of APAP. Light and electron microscopic changes were evaluated. Levels of malondialdehyde (MDA) and glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities were determined in liver tissue. RESULTS: Rats of the ethanol, saline, and RSV groups did not present any histopathological alterations. In the APAP group, we observed vascular congestion, necrosis, inflammation, sinusoidal dilatation, and loss of glycogen content. In the APAP+RSV group, these changes were markedly reduced. iNOS immunostaining showed very weak positive stained hepatocytes the sections of control, saline, and RSV groups. However, in the APAP group, iNOS immunostaining was most evident in pericentral hepatocytes. In the same areas in APAP+RSV group, intensity of iNOS immunostaining decreased. A significant increase in MDA and decreases in GSH level, CAT, and SOD activity indicated that APAP-induced hepatotoxicity was mediated through oxidative stress. Significant beneficial changes were noted in tissue oxidative stress indicators in rats treated with RSV. CONCLUSION: These biochemical, histopathological, and ultrastructural findings revealed that RSV reduced the severity of APAP-induced alterations in liver.

Effect of crocin on oxidative stress in recovery from single bout of swimming exercise in rats.

Physical exercise could cause muscle and tissue damage due to increase in the formation of free oxygen radicals during exercise. The aim of the present study was to investigate the effect of crocin on parameters associated with oxidative stress in recovery from acute swimming exercise in rats. Rats were divided into eight groups; Normal Control (NC: untreated and did not swim), Crocin Control (CC: received crocin and did not swim), Exercise-1 (Exe-1: untreated and swam), Exercise-24 (Exe-24: untreated and swam), Exercise-48 (Exe-48: untreated and swam), Exercise+Crocin-1 (Exe-Cro-1: received crocin and swam), Exercise+Crocin-24 (Exe-Cro-24: received crocin and swam), Exercise+Crocin-48 (Exe-Cro-48: received crocin and swam). AST, ALP, LDH, CK, XO enzymes levels increased after swimming in untreated and crocin-treated groups, but there was a less increase in crocin-treated groups. The highest MDA levels in serum were determined in Exe-1 compared with all other groups. There was significant difference between control and exercise groups in MDA level (p = 0.033). In contrast, there was significant difference between control and exercise groups in GSH level (p < 0.001). In addition, crocin given to swimming rats significantly increased GSH levels (p < 0.05) and decreased MDA levels when compared with untreated exercise groups. In conclusion, crocin is able to protect liver and skeletal muscle tissue against exercise-induced oxidative damage by preventing reactive oxygen species (ROS) production.

Effects of antioxidant agents against cyclosporine-induced hepatotoxicity.

BACKGROUND: To investigate the potential protective antioxidant role of ursodeoxycholic acid (UDCA), melatonin, and allopurinol treatment in cyclosporine (CsA)-induced hepatotoxicity. METHODS: Hepatotoxicity was established in Sprague-Dawley rats by daily administration of CsA. Treatment groups were additionally administered UDCA, melatonin, or allopurinol treatments. Rats that received no CsA and no treatments served as a control group. Liver samples from each group were examined by histopathologic analysis to determine the effects of CsA treatment on liver morphology. Biochemical assays were also used to determine the effect of CsA treatment on liver function, in the presence or absence of UDCA, melatonin, or allopurinol. RESULTS: CsA treatment induced hepatotoxicity, resulting in sinusoidal dilatation, congestion, infiltration, hydropic degeneration, and loss of glycogen storage in the liver. From a molecular perspective, the CsA treatment increased levels of malondialdehyde (MDA) levels, decreased levels of reduced glutathione and xanthine oxidase, and decreased activities of superoxide dismutase and catalase. The CsA treatment also resulted in decreased serum total antioxidant capacity, whereas alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin levels, and total oxidant status were increased. Treatment with UDCA, melatonin, or allopurinol reduced the CsA-induced histopathologic changes, as compared with CsA-treated samples. In addition, UDCA, melatonin, or allopurinol treatment mitigated the CsA-induced effects on glutathione and MDA levels, and on superoxide dismutase and catalase activities, as well as reduced the CsA-mediated perturbations in serum levels of total antioxidant capacity, total oxidant status, and alkaline phosphatase. CONCLUSIONS: UDCA, allopurinol, and melatonin may each help to protect against CsA-induced damage to liver tissues, possibly through effects on the antioxidant system.

Endotoxin exposure and puberty in female rats: the role of nitric oxide and caspase-1 inhibition in neonates.

Bacterial toxins are widespread in the environment as well as in the digestive system of humans and animals. Toxin from Gram-negative bacteria (endotoxin or lipopolysaccharide; LPS) has a life-long programming effect on reproduction in rats, but the mediators have not been well-documented, so we investigated the effects of LPS on the timing of puberty in female rats. Because the levels of nitric oxide (NO) and interleukin 1ß (IL-1ß) increase following injection of LPS, we injected neonates (post-natal day (pnd) 7) with LPS, with or without NO or IL-1ß inhibitors. Half of the prepubescent (pnd 30) animals received an additional LPS injection. Vaginal opening, number of ovarian follicles, and serum anti-LPS antibodies were determined. A single LPS injection was sufficient to reduce the primordial follicle pool, but puberty was delayed when rats received 2 LPS injections (at pnd 7 and 30). NO or IL-1ß inhibitors improved both of these parameters, suggesting that the early detrimental effects of LPS on puberty and primordial follicle pool are mediated by NO and IL-1ß.

Histological and biochemical effects of dexmedetomidine on liver during an inflammatory bowel disease.

Inflammation in the liver is an extraintestinal manifestation that is frequently seen during inflammatory bowel diseases (IBD). The authors investigated histopathologycal, ultrastructural and antioxidant effects of dexmedetomidine (Dex) on liver during trinitrobenzene sulfonic acid (TNBS)-induced inflammatory bowel disease. Thirty-two BALB/c mice were divided (n = 8) as follows: control; Dex (dexmedetomidine) (30 µg/kg) for 6 days; TNBS 150 µL, TNBS + ethanol (50% w/v) intrarectally; TNBS + Dex. The histopathological and ultrastructural changes were evaluated. The levels of malondialdehyde (MDA), activity of antioxidant enzymes (GPx and SOD) were measured in liver tissue. Induction of colitis induced histopathological and ultrastructural changes of damage in liver. Those changes were markedly reduced in the TNBS + Dex group and that reduction was even significant in comparison to the TNBS group. MDA levels were significantly higher in the TNBS group and dexmedetomidine significantly elevated SOD levels in the TNBS + Dex group. These results suggest that the administration of dexmedetomidine reduces the histopathological and ultrastructural damage and increases the defense capacity against oxidative damage on liver in this IBD mice model.

Protective effects of melatonin and quercetin on experimental lung injury induced by carbon tetrachloride in rats.

INTRODUCTION: Exposure to carbon tetrachloride (CCl4), a well-known toxicant, causes tissue damage by inducing oxidative stress via formation of free radicals. The fundamental structure of the organs of rats and humans is similar, so administration of CCl4 to rats is an accepted experimental model to produce oxidative damage to various tissues including pulmonary tissue. In this study, we evaluated the protective capacity of melatonin and quercetin against CCl4-induced oxidative lung damage in rats. MATERIAL-METHODS: Rats were divided into five groups each containing seven rats as follows: Control group, Olive oil group CCl4 group, CCl4+Melatonin, and CCl4+Quercetin group. The tissue samples were processed by routine histological and biochemical procedures. Sections were stained with Hematoxylin-eosin and Masson's trichrome. Histopathologic damage score was calculated. Malondialdehyde (MDA) and glutathione (GSH) levels and catalase (CAT) activities were assayed. RESULTS: The lung sections of control groups showed normal histological characteristics. Fibrosis, interstitial hemorrhage, epithelial desquamation in bronchiole and alveoli, intra-alveolar edema, leukocyte, and macrophage infiltration were observed in lung sections of rats exposed to CCl4 alone. The findings were reduced in the treatments groups. The MDA level in the CCI4 group were significantly higher than in the other groups (p < .001), and the CAT and GSH levels in the CCI4+Mel and CCI4+Quer groups were significantly higher than in the CCI4 group (p < .05). CONCLUSION: In conclusion, we suggest that agents with antioxidant properties such as melatonin and quercetin may have positive effects in the treatment of pulmonary diseases characterized by especially edema, inflammation, and fibrosis.

Once upon a time in Anatolia: the kings with bulging eyes.

The Hittite Empire, formed by the Hittites who settled in central Anatolia at the beginning of the second millennium BC, has left behind rich archeological remains. In this historical review, statues of the Hittite priest-kings, King Idrimi, King Suppiluliuma, and King Tarhunza, who ruled in these lands in ancient times, are analyzed. Graves' disease (GD) is the most common cause of hyperthyroidism. Patients with GD are also at risk of developing Graves' orbitopathy (GO). Upper eyelid retraction and exophthalmos (bulging eyes) are common in patients diagnosed with GO. Could the kings who lived in Anatolia at different times in the distant past have suffered from the same disease?

The effects of pinealectomy and melatonin treatment in acrylamide-induced nephrotoxicity in rats: Antioxidant and anti-inflammatory mechanisms.

OBJECTIVE: Acrylamide (AA) is toxic and forms in food that undergoes high-temperature processing. This study aimed to investigate the effects of AA-induced toxicity on renal tissue in pinealectomized rats and the possible protective effect of exogenous Melatonin (ML) administration. MATERIALS AND METHODS: Sixty rats were randomized into 6 groups (n = 10): Sham, Sham+AA, Sham+AA+ML, PX, PX+AA, and PX+AA+ML. Sham and pinealectomized rats received AA (25 mg/kg/day orally) and ML (0.5 ml volume at 10 mg/kg/day, intraperitoneal) for 21 days. RESULTS: The results showed that malondialdehyde (MDA), total oxidant status (TOS), oxidative stress index (OSI), tumor necrosis factor-α (TNF-α), and interleukin 1ß (IL-1ß) levels of the kidney and urea and creatinine levels of serum in the PX (pinealectomy)+AA group were more increased than in the Sham+AA group. In addition, glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and total antioxidant status (TAS) levels decreased more in the PX+AA group than in the Sham+AA group. Also, we observed more histopathologic damage in the PX+AA group. On the other hand, up-regulation of kidney tissue antioxidants, down-regulation of tissue oxidants, and improvement in kidney function were achieved with ML treatment. Also, histopathological findings such as inflammatory cell infiltration, shrinkage of glomeruli, and dilatation of tubules caused by AA toxicity improved with ML treatment. CONCLUSION: ML supplementation exhibited adequate nephroprotective effects against the nephrotoxicity of AA on pinealectomized rat kidney tissue function by balancing the oxidant/antioxidant status and suppressing the release of proinflammatory cytokines.

Crocin, the compound of the dried stigma of Crocus sativus L (saffron), restores doxorubicin-induced disturbances in kidney functioning, oxidative stress, inflammation, renal tissue morphology and TGF-ß signalling pathways.

Doxorubicin (Dox), an anthracycline antibiotic, is a chemotherapeutic drug for several cancer treatments. However, its clinical usage has been restricted because of severe side effects, including nephrotoxicity. This study aimed to demonstrate the possible nephroprotective effects of crocin (Cr) against Dox-induced oxidative stress, renal inflammation, renal morphology and transforming growth factor-ß (TGF-ß) signalling pathways in Dox-exposed rats. Hence, the rats were injected for 15 d consecutively with saline, six different injections of Dox until the cumulative dose reached 12 mg/kg., daily Cr (40 mg/kg), and Dox + Cr combination. Cr increased the activities of superoxide dismutase (SOD) and catalase (CAT), GSH content and suppressed inflammation and oxidative stress in Dox-exposed rats. Our results were confirmed by immunohistochemical findings that Cr treatment ameliorates the expressions of IL1ß and TGF-ß in Dox-induced nephrotoxicity. Conclusionally, Cr exhibits adequate nephroprotective effects against Dox-induced nephrotoxicity on rat kidney architecture and tissue function by stabilising cellular redox homeostasis, reducing renal fibrosis and suppressing inflammation.

Therapeutic Effect of Melatonin on CCl4-Induced Fibrotic Liver Model by Modulating Oxidative Stress, Inflammation, and TGF-ß1 Signaling Pathway in Pinealectomized Rats.

The study aimed to determine the CCl4-induced liver fibrosis model in pinealectomized rats and biochemically, immunohistochemically, and histopathologically investigate the therapeutic effect of melatonin on liver fibrosis. The surgical procedure for pinealectomy was performed at the beginning of the study, and the sham and pinealectomized rats were administered CCl4 dissolved in corn oil (1:1) alone every other day to induce liver fibrosis or together with melatonin (10 mg/kg) therapy for 15 days. Melatonin is an essential therapeutic agent and offers an alternative therapeutic strategy in CCl4-induced liver fibrosis by suppressing inflammation, oxidative stress, and the TGF-ß1 signaling pathway. Treatment with melatonin ameliorated CCl4-induced liver fibrosis by restoring hepatocellular damage and reducing plasma AST, ALT, and ALP values. Melatonin increases the activity of SOD and CAT, which are important enzymes for antioxidant defence, and raises GSH levels, which further enhances antioxidant function. Also, melatonin reduced hepatic inflammation (IL-6 and IL-1ß) and oxidative stress indices. Moreover, histopathological changes and immunohistochemical expression of TGF-ß1 were restored following melatonin supplementation in the CCl4-induced liver fibrosis model in pinealectomized rats. Our study shows that melatonin supplementation has a beneficial effect in protecting the liver fibrosis induced by CCl4 in pinealectomized rats.

Unveiling the placental secrets: Exploring histopathological changes and TROP2 expression in intrahepatic cholestasis of pregnancy.

INTRODUCTION: Gestational cholestasis, also known as intrahepatic cholestasis of pregnancy (ICP) or obstetric cholestasis, is a liver disease that can manifest in late pregnancy. Trophoblast cell surface antigen (TROP2) is a type I transmembrane glycoprotein identified in placental trophoblast cells that plays a critical role in trophoblast invasion of the decidua upon implantation into the placenta. Our study aims to investigate the role of TROP2 in pregnancy cholestasis. MATERIALS AND METHODS: Study groups: Group 1 (control group) (n = 10): consists of healthy normal pregnant women without any disease, Group 2 (cholestasis group) (n = 10): consists of pregnant women diagnosed with cholestasis. After routine histological follow-up, hematoxylin and eosin staining and TROP2 immunostaining were performed and scored. RESULTS: In the cholestasis group, in contrast to the control group, thrombus structures were observed in the intervillous space. In the cholestasis group compared to the control group, villus mesenchymal connective tissue cells, capillary endothelium and trophoblasts around the villus showed significantly stronger anti-TROP2 staining (p < 0.05). DISCUSSION: Cholestasis, a condition that may manifest during pregnancy, may be associated not only with observable pathological changes in placental tissues at the light microscopic level, but also with an increase in TROP2 expression. Given the critical role of TROP2 in trophoblast invasion during placental implantation, we hypothesize that TROP2 may serve as a key marker of the cholestatic processes occurring during pregnancy.

Halil Pasha's legacy as a Turkish painter: Esotropia or pseudoesotropia in "Yasli Halayik".

Introduction: Esotropia is a form of strabismus, a condition characterized by the misalignment of the eyes. Specifically, esotropia refers to inward deviation of one or both eyes. It can manifest at different ages, ranging from infancy to adulthood, and can have varying degrees of severity. The false appearance of esotropia in the alignment of the visual axes is what defines pseudoesotropia. Halil Pasha was a Turkish painter known for his contributions to the art scene during the late 19th and early 20th centuries. His artistic talent, coupled with his influential position as a statesman, allowed him to leave a lasting impact on the cultural landscape of the Ottoman Empire. Methods: In the present study, artistic depictions of esotropia or pseudoesotropia in Halil Pasha's "Yasli Halayik" were evaluated. A comprehensive literature review on strabismus in medicine and art was conducted. Results: "Yasli Halayik", translated as "Old Servant Woman", is one of the iconic paintings of Turkish art. It reflects the social dynamics and lifestyle of the time, offering a glimpse into the lives of women serving in Ottoman households. When we examine this painting as a physician, the first thing we notice is the old woman's eyes. An eye misalignment in the left eye of the old servant woman is noticed. Discussion: In medical humanities, which are addressed in medical education, medicine and art intersect with different perspectives and understandings. Although the evaluation of medical scenes in artworks seems to have been first observed by an art historian, today physicians and medical students need to examine artworks more carefully and develop their observational skills. Iconodiagnosis is the medical analysis of artworks that looks for clinical signs suggestive of medical disorders and diseases. The application of iconodiagnosis in medical education is an alternative and stimulating way to exercise students' observation skills; not only the physical examination of the patient is important, but also the information obtained from their posture, clothing, general demeanour and even physical aids.

Cytotoxic effects of Phenformin on ovarian cancer cells: expression of HIF-1α and PDK1 in the hypoxic microenvironment.

Today, many anticancer drugs are used clinically for ovarian cancer, one of the leading causes of cancer-related deaths in women. Phenformin is an antidiabetic drug of the biguanide class. It improves the antiproliferative activity in cancer cells. Hypoxia is an important component associated with ovarian cancer and its tumor microenvironment. The aim of this study was to investigate the anticancer effects of Phenformin in SKOV-3 human ovarian cancer cells under hypoxic conditions. SKOV-3 human ovarian cancer cells treated with different doses of Phenformin (0.5 mM, 1 mM, 2 mM, 5 mM) for 24 hours were subjected to WST-1 cell viability assay and Annexin V apoptosis assay. A dose-dependent decrease in cell viability with Phenformin treatment was observed. In addition, Phenformin activated percentage of apoptotic SKOV-3 cancer cells in a dose-dependent manner. In this study, Cobalt(II) chloride (CoCl2) treatment leads to increased hypoxia-inducible factor-1alpha (HIF-1α) expression and Phenformin can recover hypoxic condition. HIF-1α protein expression was significantly correlated with cell viability assay and apoptosis assay. We also found that Phenformin inhibits expression of phosphoinositide-dependent kinase 1 (PDK1) in SKOV-3 ovarian cancer cells. The ability to migrate to cancer cells was significantly reduced in a dose-dependent manner with Phenformin. This data demonstrates that Phenformin treatment can induce apoptosis and inhibit proliferation in ovarian cancer cells under hypoxic conditions. The findings reveal that HIF-1α is a new target for the treatment of ovarian cancer.

Crocin treatment exerts anti-inflammatory and anti-oxidative effects in liver tissue damage of pinealectomized diabetic rats.

Diabetes mellitus (DM) is a chronic metabolic disorder with an increasing global prevalence that leads to significant morbidity and mortality. The liver plays a vital role in glycemic regulation in physiological and pathological conditions such as DM. Free radical formation and inhibition of antioxidant defense systems play a role in the liver damage pathogenesis in diabetic patients The antioxidant, anti-diabetic, anti-inflammatory, and radical scavenging properties of crocin are known. This study was designed to determine the possible protective effects of crocin against liver tissue damage in pinealectomized diabetic rats. Sixty rats were divided into six groups: Control, Sham+streptozotocin (STZ), Pinealectomy (PINX), PINX+STZ, PINX+Crocin, and PINX+STZ+Crocin. PNX procedure was carried out on the first day of the experiment. Intraperitoneal (i.p.) injection of 50 mg/kg STZ was performed on the 30th day of the experiment to induce DM. Crocin (50 mg/kg; i.p.) was applied for 15 days after the pinealectomy procedure and induction of DM. Crocin decreased the markers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), interleukin-1ß (IL-1ß), and malondialdehyde (MDA)) of liver damage and increased antioxidant enzyme levels and tissue total antioxidant status. Histological results showed that the administration of crocin exhibited a protective effect against liver damage caused by STZ. These results indicate that crocin evidence protection against liver injury caused by STZ.

Therapeutic role of melatonin on acrylamide-induced hepatotoxicity in pinealectomized rats: Effects on oxidative stress, NF-κB signaling pathway, and hepatocellular proliferation.

Acrylamide (AA) is formed in some foods by the cooking process at high temperatures, and it could be a carcinogen in humans and rodents. The purpose of the current study was to reveal the possible protective effects of melatonin against AA-induced hepatic oxidative stress, hepatic inflammation, and hepatocellular proliferation in pinealectomized rats. Hence, the sham and pinealectomized rats were consecutively given AA alone (25 mg/kg) or with melatonin (10 mg/kg) for 21 days. Melatonin acts as an antioxidant, anti-inflammatory, and antiapoptotic agent and introduces as a therapeutic strategy for AA-induced hepatotoxicity. Melatonin supplementation reduced AA-caused liver damage by decreasing the serum AST, ALT, and ALP levels. Melatonin raised the activities of SOD and CAT and levels of GSH and suppressed hepatic inflammation (TNF-α) and hepatic oxidative stress in liver tissues. Moreover, histopathological alterations and the disturbances in immunohistochemical expression of NF-κB and Ki67 were improved after melatonin treatment in AA-induced hepatotoxicity. Overall, our results demonstrate that melatonin supplementation exhibits adequate hepatoprotective effects against hepatotoxicity of AA on pinealectomized rat liver architecture and the tissue function through the equilibration of oxidant/antioxidant status, the regulation of cell proliferation and the suppression of the release of proinflammatory cytokines.