The effect of co-administration of berberine, resveratrol, and glibenclamide on xenobiotic metabolizing enzyme activities in diabetic rat liver.

It is possible to use plant-derived antioxidant molecules in the form of dietary supplements. However, dietary supplement-drug interaction pattern has not been well defined for most of these products. The aim of this study was to determine the effects of berberine, resveratrol, and glibenclamide on xenobiotic metabolizing enzyme activities in diabetic rats. Streptozotocin was administered to create experimental diabetes. Resveratrol (5 mg/kg) (R), glibenclamide (5 mg/kg) (G), and berberine (10 mg/kg) (B) were administered individually or in combinations in DMSO by intraperitoneal administration route to the diabetic rats. DMSO was also given to non-diabetic control (C) and diabetic control (D) groups. Livers of rats were taken under anesthesia at the end of the treatment period (12 days). Ethoxyresorufin O-deethylase (EROD), pentoxyresorufin O-depentylase (PROD), aniline 4-hydroxylase (A4H), erythromycin N-demethylase (ERND), glutathione S-transferase (GST), catalase (CAT), and glutathione reductase (GR) activities were measured in microsomes and cytosols. In addition, histomorphological studies were also performed in the liver tissues. EROD activity of D+R was significantly higher than C and D+R+B. PROD activity of D+R was significantly higher than C, D, D+R+G, D+R+B, and D+R+B+ G. PROD activity of D+B was significantly higher than C and D+R+B. ERND activity of D+R was significantly higher than D+R+G and D+R+B. GST activity of D+R was significantly higher than D+R+G. CAT activity of D+B was significantly lower than C. It is clear that co-administration of resveratrol, berberine, and glibenclamide modifies some of the important xenobiotic metabolizing enzyme activities. Resveratrol and berberine have the potential to cause dietary supplement-drug interaction.

Decreasing myocardial estrogen receptors and antioxidant activity may be responsible for increasing ischemia- and reperfusion-induced ventricular arrhythmia in older female rats.

AIMS: This study aimed to investigate the relationship between ischemia- and reperfusion-induced arrhythmia and blood serum estrogen levels, myocardial estrogen receptor levels, antioxidant enzyme activities, and the effects of the estrogen receptor blocker, fulvestrant (ICI 182 780). MAIN METHODS: A total of 102 female Sprague-Dawley rats of different ages (2-3, 6-7, 14-15, and 20-21 months) were used in this study. Myocardial ischemia was produced by ligation of the descending branch of the left anterior descending coronary artery, and reperfusion was produced by releasing this artery. An electrocardiogram (ECG) and blood pressure were recorded for 6 min of ischemia and 6 min of reperfusion. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), estrogen receptor α (ERα), and estrogen receptor ß (ERß) in myocardial tissue and 17 beta-estradiol (E2) in blood serum were measured via enzyme-linked immunosorbent assay (ELISA). The results were compared using a Mann-Whitney U test, one-way analysis of variance (ANOVA), and a student's t-test. KEY FINDINGS: It is not the changes in serum estrogen levels but the decreasing myocardial estrogen receptors and antioxidant activities that could be responsible for the occurrence of more severe arrhythmia in response to reperfusion in older female rats. SIGNIFICANCE: The death rate due to a heart attack in younger men is higher than in women. However, it equalizes after the menopausal stage in women. In this study, the reason for the increasing sudden post-menopausal death rate in women was investigated experimentally.

Monitoring of pollution in the western Black Sea coast of Turkey by striped red mullet (Mullus surmuletus).

The striped red mullet (Mullus surmuletus) is an economically important demersal fish species. In this study, our aim was to monitor the pollution in the western Black Sea coast of Turkey using striped red mullet as a bioindicator species. Fish samples were caught from four different locations in the western Black Sea coast of Turkey in 2006, 2009-2011, and 2016. Highly elevated cytochrome P4501A (CYP1A)-related 7-ethoxyresorufin O-deethylase (EROD) activities were measured in striped red mullet caught from Zonguldak Harbor in all of the sampling years. The lowest EROD activities were measured in fish samples caught from Kefken. In addition to the EROD activity measurements, glutathione S-transferase (GST), glutathione reductase, and catalase activities were also measured in the striped red mullet samples. Higher GST and catalase activities were measured in the striped red mullet samples caught from Zonguldak Harbor than from Kefken in 2016. These results indicate that the striped red mullet is responsive to CYP1A inducer pollutants. This study covers intermittent measurements of the biomonitoring data from the striped red mullet caught around the western Black Sea coast of Turkey, over a 10-year period.

Modulation of xenobiotic metabolizing enzyme activities in rat liver by co-administration of morin, endosulfan, and 7,12-dimethylbenz[a]anthracene.

Morin is a flavonoid which is present in many plants. Endosulfan and 7,12-dimethylbenz[a]anthracene (DMBA) are toxic chemicals that humans are exposed to in their daily lives. In this study, the protective role of morin was investigated in endosulfan and DMBA treated rats. Eight groups, each comprising seven 2.5-month-old adult male Wistar rats (weighing 170-255 g), were used. Endosulfan, morin, and DMBA were administered individually or in combinations, at 5 mg/kg body weight (bw) (three times/week), 25 mg/kg bw (three times/week), and 30 mg/kg bw (once/week for three weeks) via oral gavage, respectively. On day 54 of the administration period, the rats were killed. DMBA + endosulfan co-administration significantly increased CYP1A1-, CYP1A2-, CYP2E-, and GST-associated activities in the rats compared to the control. DMBA + endosulfan + morin significantly increased CYP1A1, CYP1A2, CYP3A, and GST associated activities in the rats relative to the control. Histopathological studies were performed to investigate protective effects of morin on liver damage. The results indicated that DMBA + endosulfan treatment induced liver damage, and morin reduced this damage. These findings suggest that CYP1A, CYP3A, and GST enzyme activities participate in the protective mechanism of morin against endosulfan and DMBA induced toxicity.

Combined use of PAH levels and EROD activities in the determination of PAH pollution in flathead mullet (Mugil cephalus) caught from the West Black Sea coast of Turkey.

The aim of this study was to determine the extent of polycyclic aromatic hydrocarbon (PAH) pollution by measuring PAH levels and 7-ethoxyresorufin-O-deethylase (EROD) activities in flathead mullet (Mugil cephalus) samples caught from the West Black Sea coast of Turkey. The fish samples were caught in August 2008-2011. The levels of 13 PAHs were measured by high-performance liquid chromatography (HPLC) in the liver of fish. Most of the measured PAHs had three rings (low molecular weight). The frequencies of detection of PAHs were higher in fish samples caught from Zonguldak Harbour and Gülüç Stream Mouth than those from Sakarya River Mouth, Amasra and Kefken. EROD activities and cytochrome P4501A (CYP1A) protein level were also measured in the fish liver microsomes. Highly elevated EROD activities and CYP1A levels were measured in the mullet samples caught from Zonguldak Harbour and Gülüç Stream than those from Amasra and Kefken. The detection of PAHs in the liver of fish samples shows recent exposure to PAHs. The chemical analyses of PAHs and EROD activity results together reflected the extent of PAH pollution in the livers of fish caught from the West Black Sea coast of Turkey. The results indicate that Zonguldak Harbour is the most polluted site in the West Black Sea coast of Turkey.

Determination of organochlorine pesticide concentrations in flathead mullet (Mugil cephalus) caught from the western Black Sea coast of Turkey.

The objective of this study was to determine the levels of 14 organochlorine pesticides (OCPs) in flathead mullet (Mugil cephalus) caught from the western Black Sea coast of Turkey. The fish samples were caught from five different locations of the western Black Sea coast of Turkey in August 2009. Organochlorine pesticides were extracted from the liver tissues, and then the levels of OCPs were measured using gas chromatography with an electron capture detector. Organochlorine pesticides were detected in all locations. The levels of total OCPs in fish samples ranged between 0.224 and 1.103 µg g(-1) dry weight in the western Black Sea coast of Turkey. DDT, beta-HCH, and endosulfan I were the dominant OCPs in the fish samples. The levels of DDT in fish samples ranged between 0.081 and 0.186 µg g(-1) dry weight. The levels of total HCH in fish samples ranged between 0.007 and 0.376 µg g(-1) dry weight in the western Black Sea coast of Turkey. Although the usage of OCPs was banned in Turkey, the results of this study clearly indicated the presence of OCPs in the western Black Sea coast of Turkey and exposure of living organisms to these chemicals.

Aldrin epoxidation in flathead mullet (Mugil cephalus): possible involvement of CYP1A and CYP3A.

The primary objective of this study was to determine specific cytochrome P450 isozyme(s) involved in the metabolism of aldrin to its toxic metabolite dieldrin in flathead mullet (Mugil cephalus) liver microsomes. To identify the cytochrome P450 isozyme responsible for the aldrin metabolism in mullet liver, the effects of mammalian-specific cytochrome P450 inhibitors and substrates were determined in the epoxidation reaction of aldrin. CYP3A-related inhibitors, ketoconazole, SKF-525A, and cimetidine, inhibited the metabolism of aldrin. The contribution of CYP1A to the aldrin metabolism was shown by the inhibition of 7-ethoxyresorufin-O-deethylase activity in the presence of aldrin. The results indicate that CY1A and CYP3A are the cytochrome P450s involved in aldrin epoxidase activity in mullet. In addition, the suitability of aldrin epoxidase activity for monitoring of environmental pollution was also assessed in the fish samples caught from four different locations of the West Black Sea coast of Turkey.

Assessment of pollution in the West Black Sea Coast of Turkey using biomarker responses in fish.

Aim of this study was to determine the extent of pollution in the West Black Sea Coast of Turkey by measuring CYP1A associated EROD activity, phase II enzyme, glutathione S-transferase and antioxidant enzymes, catalase and glutathione reductase activities and immunochemical detection of CYP1A protein level in the liver of mullet. The fish samples were caught from six locations having a varying degree of pollution in the West Black Sea Region of Turkey in August 2005, 2006 and 2007. Mullets caught from Zonguldak Harbour, Eregli Harbour and Gülüç Stream's Mouth displayed 6-9-fold higher EROD, 2-4-fold higher glutathione S-transferase and 2-3-fold higher catalase activities than the reference site, Amasra. Total polyaromatic hydrocarbon levels in mullets caught from these locations were also significantly higher (2-4-fold) than Amasra. The results of this study indicate that Zonguldak Harbour, Eregli Harbour and Gülüç Stream are highly polluted by polycyclic aromatic hydrocarbons and related contaminants.