A Comparative Study for the Evaluation of Two Doses of Ellagic Acid on Hepatic Drug Metabolizing and Antioxidant Enzymes in the Rat

The present study was designed to evaluate different doses of ellagic acid (EA) in vivo in rats for its potential to modulate hepatic phases I, II, and antioxidant enzymes. EA (10 or 30 mg/kg/day, intragastrically) was administered for 14 consecutive days, and activity, protein, and mRNA levels were determined. Although the cytochrome P450 (CYP) 2B and CYP2E enzyme activities were decreased significantly, the activities of all other enzymes were unchanged with the 10 mg/kg/day EA. In addition, western-blot and qRT-PCR results clearly corroborated the above enzyme expressions. On the other hand, while the NAD(P)H:quinone oxidoreductase 1 (NQO1), catalase (CAT), glutathione peroxidase (GPX), and glutathione S-transferase (GST) activities were increased significantly, CYP1A, 2B, 2C, 2E, and 19 enzyme activities were reduced significantly with 30 mg/kg/day EA. In addition, CYP2B, 2C6, 2E1, and 19 protein and mRNA levels were substantially decreased by the 30 mg/kg/day dose of EA, but the CYP1A protein, and mRNA levels were not changed. CYP3A enzyme activity, protein and mRNA levels were not altered by neither 10 nor 30 mg/kg/day ellagic acid. These results indicate that EA exerts a dose-dependent impact on the metabolism of chemical carcinogens and drugs by affecting the enzymes involved in xenobiotics activation/detoxification and antioxidant pathways

Effects of Cyclamen trochopteranthum on hepatic drug-metabolizing enzymes

The modulatory effects of the Cyclamen trochopterantum tuber extract on hepatic drug-metabolizing enzymes, including aniline 4-hydroxylase (A4H; CYP2E1), ethoxyresorufin O-deethylase (EROD; CYP1A), methoxyresorufin O-demethylase (MROD; CYP1A), caffeine N-demethylase (C3ND; CYP1A2) aminopyrene N-demethylase (APND; CYP2C6), and erythromycin N-demethylase (ERND; CYP3A1), were examined in vivo in rats. The activities of all of these enzymes were induced by the cyclamen extract. In addition, Western-blot and RT-PCR results clearly showed that CYP2E1, CYP1A1/CYP1A2 and CYP2C6 protein and mRNA levels were substantially increased by four different doses of cyclamen. Although, the CYP3A1 protein level was increased significantly, the mRNA level was not changed. These results indicate that cyclamen tuber extract might have a potential not only to inhibit and/or induce the metabolism of certain co-administered drugs but also influence the development of toxicity and carcinogenesis due to the induction of the cytochrome P450-dependent drug-metabolizing enzymes

Erratum to “A Comparative Study for the Evaluation of Two Doses of Ellagic Acid on Hepatic Drug Metabolizing and Antioxidant Enzymes in the Rat”

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Inula viscosa INDUCES THE p53-DEPENDENT CELL DEATH PATHWAY IN BREAST CANCER CELLS

Failure to activate cell death mechanisms in response to drug therapy used for breast cancer may lead to drug resistance. Therefore, knowledge of cell death mechanisms is essential for drug therapy and strategies targeting drug resistance. Although Inula viscosa (IV), widely used as a medicinal plant for traditional therapeutic purposes, can induce apoptosis in many cancers cell lines, its molecular mechanisms are not fully understood. Here, a report was presented on the apoptotic mechanism of IV in breast cancer cells. To this end, cytotoxicity of IV in breast cancer cell lines was assigned by crystal violet staining assay. RT-PCR, Western blot analysis, Annexin V-FITC apoptosis detection, p53RE luciferase assay, and p73 siRNA technique were used to evaluate the apoptotic mechanism of IV. The results indicated that N showed dose-dependent cytotoxic effects in breast cancer cell lines and induced apoptosis. As a result of IV treatment, Apaf1, Bax, Caspase 8 and 9, p53, and p73 mRNA expressions were up-regulated, but Bcl-2 gene expression level was down-regulated. In addition, it was observed that IV increased the p53 luciferase activity. Fewer cells underwent apoptosis after p73 siRNA transfection. In conclusion, IV may play a role in p53-dependent caspase activation in breast cancer cells and may also induce apoptosis in p53-mutated breast cancer cells by partially targeting p73.Pamukkale University [2019BSP021]This work received a grant by the Pamukkale University (2019BSP021). I would like to thank Professor Dr. Giirkan Semiz for collecting and identifying plants

Biochemical, pharmacological, and toxicological attributes of caper (Capparis ovata) flowering buds and berries pickles

Capparis ovata is a natural plant that grows widely in Turkey and its flowering buds and berry pickle are used in traditional medicine. Thus, the current study was expanded to evaluate the biochemical, pharmacological, and toxicological aspects of the Capparis ovata water extract (COWE). To determine the biochemical properties of COWE, mineral and fatty acid content, elemental analysis, flavonoid/phenolic content, radical-scavenging capacity, and pesticide analysis were performed. Furthermore, to find out whether it had anti-inflammatory properties, reverse transcription-polymerase chain reaction (RT-PCR) and nuclear factor kappa B (NF-κB) luciferase activity tests were conducted. Whole-genome transcriptomic profiling was carried out at a dose level of 500 mg/kg COWE to understand its pharmacological effect. Transaminases in serum were tested, and quantitative polymerase chain reaction (qPCR) was done using a custom design array that included the stress and molecular toxicology pathway to establish its toxicological qualities. As a result of the evaluations, it was observed that COWE has a high mineral and unsaturated fatty acid content, flavonoid/phenolic content, and radical-scavenging ability. It significantly inhibited NF-κB transcriptional activity as well as inflammatory cytokine expression in T-lymphoblast cells. Whole-genome transcriptomic profiling depicted that COWE modulates immune responses by upregulating natural killer cell activation, cellular response to type I interferon, B-cell proliferation and differentiation, and Janus kinase–signal transducer and activator of transcription (JAK–STAT) pathways. Molecular Toxicology Pathfinder RT2 Profiler PCR array analysis revealed that COWE at or lower dose of 500 mg/kg/day did not cause a comparatively adverse effect. According to the findings, COWE is a rich source of nutrients and can be used as an adjunct therapy for various inflammatory diseases

Investigation of the Effects of Platelet-rich Plasma on Surgically Created Temporomandibular Joint Cartilage Defects: An Experimental Animal Study

Background: Temporomandibular joint (TMJ) disorders are characterized by symptoms such as pain, clicking sound, and crackling in the jaw joint during chewing or mouth opening. Platelet-rich plasma (PRP) is a cellular plasma component obtained from whole blood, containing high platelet concentration and hyperphysiological growth factors. The aim of our study was to evaluate the effects of PRP on surgically created TMJ cartilage defects. Materials and Methods: A total of 12 adult New Zealand rabbits (2500–3000 g) were included in the study. Full-thickness osteochondral defects were created by dividing into two groups as right TMJ joint group (experimental group; Group I) and the left TMJ joint group (control group; Group II). Full-thickness osteochondral defects were created on both sides, and PRP was applied to Group 1 and saline was applied to Group 2. After 1 week, both PRP and saline were readministered. Results: The subjects were sacrificed under general anesthesia 4 weeks later, and bilateral condylar heads were surgically removed. Although there was a histological and macroscopic difference between the groups, no significant difference was found. Conclusion: More comprehensive studies should be conducted by increasing the follow-up time, frequency, and number of PRP applications. In this experimental study, the application of PRP gave effective results

In vivo examination of the effects of hydroxycinnamic acid on xenobiotic metabolizing and antioxidant enzymes

In the last decade, hydroxycinnamic acids (HCA) have gained increasing attention from researchers due to their antioxidant potential. The aim of this study was to examine in detail the impact of dietary HCA on particular types of P450 and also selected phase II and antioxidant enzymes in Wistar rat. HCA (10 mu M/kg/day, i.p.) was administered for ten continuous days. Examination of the activities and mRNA and protein levels revealed that CYP2B, 2C6 and 3A enzyme activities were not altered significantly, with Western blot and qRT-PCR results corroborating this result. While treatment with HCA led to a significant reduction in CYP1A1/CYP1A2-associated enzyme activities, CYP1A1 protein, and mRNA levels were found to be unchanged. Aromatase (CYP19) activity, as well as protein and mRNA levels, were significantly reduced with HCA treatment. On the other hand, the NAD(P) H: quinone oxidoreductase 1 (NQO1), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferases (GSTs) activities were increased significantly. Also, HCA treatment significantly increased the GST-mu and GST-theta mRNA levels

Epilobium hirsutum alters xenobiotic metabolizing CYP1A1, CYP2E1, NQO1 and GPx activities, mRNA and protein levels in rats

Context: Natural products have attracted increasing interests due to their use in flavoring, nutrition, cosmetics, pharmacy and medicine. Epilobium hirsutum L. (Onagraceae) is known for its analgesic, antimicrobial, and antiproliferative activity. CYP1A1 and CYP2E1, xenobiotic metabolizing enzymes, serve as a metabolic activation route yielding reactive metabolites that are eliminated by the action of NQO1 and glutathione peroxidase (GPx) enzymes

In vivo examination of the effects of hydroxycinnamic acid on xenobiotic metabolizing and antioxidant enzymes

In the last decade, hydroxycinnamic acids (HCA) have gained increasing attention from researchers due to their antioxidant potential. The aim of this study was to examine in detail the impact of dietary HCA on particular types of P450 and also selected phase II and antioxidant enzymes in Wistar rat. HCA (10 mM/kg/day, i.p.) was administered for ten continuous days. Examination of the activities and mRNA and protein levels revealed that CYP2B, 2C6 and 3A enzyme activities were not altered significantly, with Western blot and qRT-PCR results corroborating this result. While treatment with HCA led to a significant reduction in CYP1A1/CYP1A2-associated enzyme activities, CYP1A1 protein, and mRNA levels were found to be unchanged. Aromatase (CYP19) activity, as well as protein and mRNA levels, were significantly reduced with HCA treatment. On the other hand, the NAD(P)H:quinone oxidoreductase 1 (NQO1), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferases (GSTs) activities were increased significantly. Also, HCA treatment significantly increased the GST-mu and GST-theta mRNA levels. These observations may be of importance given the potential use of HCA as a chemopreventive and as an anticancer agent