Profenofos as an organophosphorus insecticide has been used in the agricultural countries as Egypt, may find its way to water system and adversely effect on aquatic life particularly fish. Nile tilapia, Oreochromis niloticus as a major fish species in River Nile and one of the major sources of protein for human beings in Egypt, and it can also be a source of threaten to human health. Transport profenofos directly to tilapia fish may affect their physiological status and then fish production. The mortality of profenofos toxicity was estimated on tilapia and LC50 was detected as 0.87 mg/l. Also fish were exposed to 1/2 LC50 for 96 hrs and to 1/10 LC50 for 28 days and lastly were left after the chronic toxicity for another 28 days as recovery period. The increase of blood glucose was accompanied with decrease in liver and muscles glycogen throughout the acute and chronic trail periods. Fish showed also highly significant decrease in serum total protein and globulin with increasing in albumin and A/G ratio. A sharp elevation in serum creatinine, urea and uric acid with decrease in serum total lipid, triglyceride and cholesterol were also recorded. Lastly gradual and sharp elevation in the levels of serum enzymes, S-AST, S-ALT and S-ALP was revealed in profenofos-exposed tilapia. Same behavior as S-AST and S-ALT were in liver transaminases (L-AST & L-ALT). Our study revealed adverse change of metabolism in tilapia due to profenofos exposure. This may inform about the dangerous use of profenofos and limitations should be managed.

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It is known that xanthine oxidoreductase contributes significantly to ischemia/reperfusion injury by generating reactive oxygen species. Ischemia-modified albumin (IMA) is a biomarker of acute myocardial ischemia with high sensitivity but moderate specificity. Our study aims to evaluate the xanthine oxidase (XO) system and the IMA level in the serum of patients with ischemic heart disease, and their correlation with traditional cardiac markers. The study was conducted on 60 patients with ischemic heart disease and 22 healthy subjects (control group). Subjects were divided into three groups: group I (30 patients with ST-elevated myocardial infarction), group II (30 patients with chronic stable angina), and the control group (22 subjects). The patients and controls had laboratory tests performed including lipid profile, cardiac enzymes, XO, uric acid, and IMA. The serum levels of XO and IMA were significantly higher in group I (1.65 ± 0.29 U/ml and 0.58 ± 0.15 ABSU, respectively) than in group II (1.11 ± 0.20 U/ml and 0.29 ± 0.10 ABSU, respectively) and the control group (0.95 ± 0.16 U/ml and 0.24 ± 0.08 ABSU, respectively) (P < 0.001). There was a significant positive correlation between XO and IMA in group I. Also, there was significant positive correlation between XO or IMA and other cardiac markers, with the highest level of significance between IMA and creatine kinase (CK-MB). In group II only XO activity was significantly elevated in comparison with controls. These results confirm the role of XO enzyme in ischemic heart disease with involvement of IMA, at a detectable level, during the early necrotic phase.

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Diabetes is the most common endocrine disorder contributing to high morbidity and mortality globally. Due to the side effects reported for anti-diabetic drugs, there is a rising interest in herbal medicine for diabetes mitigation. However, rare studies were performed to analyze the molecular effects of natural agents on diabetes. Therefore, this study is the first to assess the possible ameliorating effects of avocado and cinnamon extracts on streptozotocin (STZ)-induced disturbances in the gene expression of PDX1 and Ins1 in type-2 diabetic rats, in comparison to metformin. A total number of 50 male Albino rats were randomly divided into five groups; normal control, STZ-induced diabetic group (65 mg/kg b.w divided into three doses 5 days apart), three other STZ-

Diabetic nephropathy (DN) is one of the most serious complications of diabetes mellitus. Our study aims to demonstrate the effectiveness of exenatide, glucagon like peptide-1 receptor agonist, on insulin release and renal functions in type 2 diabetes mellitus (T2DM) rats enduring DN. T2DM was induced in male wistar-albino rats by single streptozotocin injection (40 mg/kg, i.p.) followed by high fat diet for 10 weeks, while the treatment group received exenatide injection (10 µg/kg/day, i.p.) one week after STZ injection along for 9 weeks. Animals were monitored by periodic biochemical testing of fasting serum glucose (FSG), cystatin-C, creatinine and urinary protein levels. At the end of the study (10 weeks) serum total nitrite/nitrate (NO x) , adiponectin, C-peptide and amylase activity were investigated. Renal total triglycerides; hydroxy proline (HP), and DNA fragmentation were estimated, as well as renal enzymatic activity and mRNA expression level of glucose-6-phosphatase. Exenatide showed significant reduction in FSG, serum creatinine, cystatin-C, and urinary protein levels in diabetic rats. It favored increased serum NO x , serum adiponectin as well as C-peptide which reflects improving in insulin sensitivity and release respectively. Further, exenatide diminished renal DNA fragmentation, decreased renal triglyceride, HP contents, and glucose-6-phosphatase enzyme activity and expression levels in diabetic rats. Our data donate further credence for the effectiveness of exenatide against diabetic renal complications, through different aspects including reduction of renal DNA fragmentation and gluconeogenesis in addition to the previously reported mechanisms.

Panitumumab is an approved monoclonal antibody for the treatment of colorectal cancer (CRC); however, mutations in EGFR signaling pathway resulted in poor response. Schisandrin-B (Sch-B) is a phytochemical that was suggested to protect against inflammation, oxidative stress, and cell proliferation. The present study aimed to investigate the potential effect of Sch-B on panitumumab-induced cytotoxicity in wild-type Caco-2, and mutant HCT-116 and HT-29 CRC cell lines, and the possible underlying mechanisms. CRC cell lines were treated with panitumumab, Sch-B, and their combination. The cytotoxic effect of drugs was determined by MTT assay. The apoptotic potential was assessed in-vitro by DNA fragmentation and caspase-3 activity. Additionally, autophagy was investigated via microscopic detection of autophagosomes and quantitative reverse transcriptionpolymerase chain reaction (qRT-PCR) measurement of Beclin-1, Rubicon, LC3-II, and Bcl-2 expression. The drug pair enhanced panitumumab cytotoxicity in all CRC cell lines where IC50 of panitumumab was decreased in Caco-2 cell line. Apoptosis was induced through caspase-3 activation, DNA fragmentation, and Bcl-2 downregulation. Caco-2 cell line treated with panitumumab showed stained acidic vesicular organelles, contrariwise, all cell lines treated with Sch-B or the drug pair displayed green fluorescence indicating the lack of autophagosomes. qRT-PCR revealed the downregulation of LC3-II in all CRC cell lines, Rubicon in mutant cell lines, andBeclin-1 in HT-29 cell line only. Sch-B at 6.5 µM promoted panitumumab-induced apoptotic cell death, in-vitro, via caspase-3 activation and Bcl-2 downregulation, rather than autophagic cell death. This novel combination therapy against CRC, allows the reduction of panitumumab dose to guard against its adverse effects.

Objectives Cyclophosphamide (CPA) is highly effective in treating several human tumours and autoimmune disorders; but, it triggers deleterious side effects. Avocado, Persea americana (Mill.), is a widely consumed fruit with pronounced nutritional and medicinal value. Though many studies examined the protective mechanisms of natural products against CPA toxicity, almost none investigated the modulation of CPA metabolism as a potential underlying mechanism for protection. Here, we investigated the modulating effect of avocado extract (AE) on certain CPA metabolizing enzymes and its correlation with the extent of CPA-induced pulmonary toxicity and urotoxicity. Methods Rats received oral AE (0.9 g/kg body weight/day) 7 days before a single CPA injection (150 mg/kg body weight) and continued AE intake for 2, 7 or 28 days to study three phases of CPA-induced urotoxicity and pulmonary toxicity. Key findings CPA acutely elevated then reduced hepatic microsomal cytochrome P450 2B6 (CYP2B6) content and significantly suppressed bladder and lung glutathione-S-transferase activity. Furthermore, CPA elevated lung myeloperoxidase activity, DNA content and hydroxyproline level and bladder blood content. AE ameliorated CPA-induced derangements through suppression of CYP2B6 and myeloperoxidase and augmentation of glutathione-S-transferase activity in CPA-treated rats. Conclusions AE modulation of CPA metabolizing enzymes and potential anti-inflammatory effect may mitigate CPA-induced toxicity.