This study is aimed at assessing the antihyperglycemic, antihyperlipidemic, and antioxidant effects of Citrus reticulata (C. reticulata) fruit peel hydroethanolic extract and two flavonoids, ...hesperidin and quercetin, in nicotinamide (NA)/streptozotocin- (STZ-) induced type 2 diabetic rats. In addition, GC-MS and HPLC-MS analyses of the extract were performed and the results indicated the presence of multiple flavonoids including hesperidin, quercetin, naringin, and polymethoxylated flavones (nobiletin and tangeretin). To achieve the aim of the study, diabetic rats with NA/STZ-induced T2DM were orally treated with C. reticulata fruit peel hydroethanolic extract, hesperidin, and quercetin at a dose of 100 mg/kg b.w./day for four weeks. The treatments with C. reticulata fruit peel extract, hesperidin, and quercetin significantly ameliorated the impaired oral glucose tolerance; the elevated serum fructosamine level; the diminished serum insulin and C-peptide levels; the altered HOMA-IR, HOMA-IS, and HOMA-β cell function; the decreased liver glycogen content; the increased liver glucose-6-phosphatase and glycogen phosphorylase activities; the deleteriously affected serum lipid profile; the elevated serum AST and ALT activities; and the raised serum creatinine and urea levels in the diabetic rats. The treatments also produced remarkable improvement in the antioxidant defense system manifested by a decrease in the elevated liver lipid peroxidation and an increase in the lowered glutathione content and GPx, GST, and SOD activities. Furthermore, the three treatments enhanced the mRNA expression of GLUT-4 and the insulin receptor β-subunit, but only quercetin produced a significant increase in the expression of adiponectin in adipose tissue of diabetic rats. In conclusion, C. reticulata fruit peel hydroethanolic extract, hesperidin, and quercetin have potent antidiabetic effects which may be mediated through their insulinotropic effects and insulin-sensitizing actions. In addition, the alleviation of the antioxidant defense system by the extract, hesperidin, and naringin may have an important action to enhance the antidiabetic actions and to improve liver and kidney functions in NA/STZ-induced diabetic rats.
Background
The current standard of care for patients with chronic hepatitis C virus (HCV) infection is a combination of direct-acting antiviral agents (DAAs). However, rare clinical trials have been ...reported on the combination regimen of sofosbuvir (SOF) with ombitasvir, paritaprevir, and ritonavir (OBV/PTV/r) plus ribavirin (RBV) for treated patients with HCV genotype 4 (GT4) infection.
Aims
To clarify the retreatment efficacy and safety of the recent regimen, SOF with OBV/PTV/r + RBV, for chronic HCV GT4-experienced patients who failed treatment with DAA-based regimens.
Methods
A total of 113 treatment-experienced patients were allocated for the completion of their treatment period. The enrolled patients were treated orally with SOF plus a fixed dose combination of OBV/PTV/r + RBV, which was administered orally based on the patients’ tolerability. The primary end point was a sustained virological response (HCV RNA < 15 IU/mL), observed 12 weeks after the end of the treatment (SVR12).
Results
Among all patients, the treatment-experienced patients with SOF plus OBV/PTV/r + RBV had a higher SVR12 rate (97%; 109/113). Further, SVR12 was achieved by 98% (81/83) of non-cirrhotic patients and 93% (28/30) of cirrhotic patients. Additionally, the most common adverse events reported included fatigue, headache, insomnia, nausea, and dyspnea.
Conclusions
The recent multi-targeted regimen of SOF plus OBV/PTV/r + RBV was well tolerated and achieved excellent SVR rates among retreatment-experienced Egyptian patients with prior DAA treatments failure, thus providing an alternative regimen for the retreatment of difficult-to-cure HCV GT4 patients.
Background
The long-term effects of diabetes mellitus (DM) can impair several organs, including the kidney, resulting in serious health problems. Diabetic nephropathy (DN), a primary contributor in ...end-stage renal failure worldwide, affects 20–30% of patients with type 2 DM (T2DM). This study was designed to assess the contribution of nuclear factor kappa B (NF-
κ
B) and interleukin (IL)-6, IL-19, IL-34, and IL-37 in the development of DN.
Methods
The study included 160 participants, of which 130 were allocated into the patients with diabetes group, patients with chronic kidney disease (CKD), and patients with diabetic chronic kidney disease (DCKD), and 30 were healthy controls.
Results
The obtained data revealed a significant (
p
< 0.05) increase in IL-19, IL-34, and NF-
κ
B mRNA expression and serum IL-6 levels in patient groups (CKD and DCKD) compared with the healthy control group, whereas IL-19, IL-34, and NF-
κ
B mRNA expression showed a marked elevation in the DCKD group when compared with patients with CKD. Conversely, IL-37 mRNA expression and serum superoxide dismutase (SOD) activity were significantly (
p
< 0.05) decreased in both groups relative to the healthy controls, whereas the decrease was markedly higher in the DCKD group when compared with the CKD group.
Conclusion
The obtained results could indicate the potential implication of NF-
κ
B, IL-19, IL-34, and IL-6 levels, along with the decrease in IL-37 expression and serum SOD activity, in the pathophysiology of kidney disease in diabetes. Moreover, designing drugs targeting these cytokines and/or their signal pathways may prevent or alleviate the progression of kidney disease.
Diabetes mellitus (DM) is a chronic metabolic disorder that threatens human health. Medicinal plants have been a source of wide varieties of pharmacologically active constituents and used extensively ...as crude extracts or as pure compounds for treating various disease conditions. Thus, the aim of this study is to assess the anti-hyperglycemic and anti-hyperlipidemic effects and the modes of action of the aqueous extracts of the fruits and seeds of
(
.
) in nicotinamide (NA)/streptozotocin (STZ)-induced diabetic rats. Gas chromatography-mass spectrometry analysis indicated that 3,4,6-tri-O-methyl-d-glucose and 9,12-octadecadienoic acid (Z,Z)- were the major components of the
.
fruit and seed extracts, respectively. A single intraperitoneal injection of STZ (60 mg/kg body weight (b.w.)) 15 min after intraperitoneal NA injection (60 mg/kg b.w.) was administered to induce type 2 DM. After induction was established, the diabetic rats were treated with the
.
fruit and seed aqueous extracts (200 mg/kg b.w./day) via oral gavage for 4 weeks. As a result of the treatments with the
.
fruit and seed extracts, the treated diabetic-treated rats exhibited a significant improvement in the deleterious effects on oral glucose tolerance; serum insulin, and C-peptide levels; liver glycogen content; liver glucose-6-phosphatase and glycogen phosphorylase activities; serum lipid profile; serum free fatty acid level; liver lipid peroxidation; glutathione content and anti-oxidant enzyme (glutathione peroxidase, glutathione-S-transferase, and superoxide dismutase) activities; and the mRNA expression of the adipose tissue expression of the insulin receptor β-subunit. Moreover, the treatment with fruit and seed extracts also produced a remarkable improvement of the pancreatic islet architecture and integrity and increased the islet size and islet cell number. In conclusion, the
.
fruit and seed aqueous extracts exhibit potential anti-hyperglycemic and anti-hyperlipidemic effects, which may be mediated by increasing the serum insulin levels, decreasing insulin resistance, and enhancing the anti-oxidant defense system in diabetic rats.
Ticks were collected from ruminants in various areas of Sudan in 1998 and 2000. Primer pairs of rickettsial citrate synthase gene (gltA) and a spotted fever group (SFG) rickettsial 190-kDa surface ...antigen gene (rompA), respectively, were used for identification. Polymerase chain reaction (PCR)-positive products were used for DNA sequencing. The gltA gene was detected in 55% of the ticks examined (57/104). Among the 57 ticks studied, 19 were positive for the rompA gene. Thus, 18% of the ticks examined were found to be infected with SFG rickettsiae. The nucleotide sequences of the amplified rompA gene fragment of Hyalomma spp. and Amblyomma spp. were similar to those of Rickettsia aeschlimannii and Rickettsia africae, respectively. In this study, we succeeded in detecting the SFG rickettsiae gene in ticks, and established that there were at least two species of SFG rickettsiae in field ticks in Sudan.
The present study aimed to evaluate the antihyperglycemic effects of Musa paradisiaca (M. paradisiaca) leaf and fruit peel hydroethanolic extracts and to suggest their probable mode of actions in ...nicotinamide (NA)/streptozotocin (STZ)-induced diabetic rats. The leaf and fruit peel hydroethanolic extracts were analyzed by GC-MS that indicated the presence of phytol, octadecatrienoic acid, hexadecanoic acid, and octadecadienoic acid as major components in the leaf extract and vitamin E, octadecenamide, β-sitosterol, and stigmasterol as major phytochemicals in the fruit peel extract. Diabetes mellitus was induced by a single intraperitoneal injection of STZ (60 mg/kg body weight) dissolved in citrate buffer (pH 4.5), 15 minutes after intraperitoneal injection of NA (120 mg/kg body weight). The NA/STZ-induced diabetic rats were, respectively, treated with M. paradisiaca leaf and fruit peel hydroethanolic extracts at a dose of 100 mg/kg body weight/day by oral administration for 28 days. The treatment of NA/STZ-induced diabetic rats with leaf and fruit peel extracts significantly improved the impaired oral glucose tolerance and significantly increased the lowered serum insulin and C-peptide levels. The HOMA-IR (as the index of insulin resistance) and QUICKI (as a marker for insulin sensitivity), as well as HOMA-β cell function were significantly alleviated as a result of treatment of diabetic rats with leaf and fruit peel extracts. In association, the elevated serum-free fatty acids, TNF-α, and IL-6 levels were significantly decreased. In addition, the suppressed adipose tissue PPARγ, GLUT4, adiponectin, and insulin receptor β-subunit mRNA expressions were upregulated while the elevated adipose tissue resistin expression was downregulated in diabetic rats as a result of treatment with the leaf and peel extract. Based on these results, it can be concluded that M. paradisiaca leaf and fruit peel hydroethanolic extracts have antihyperglycemic effects which may be mediated via their insulinotropic and insulin-sensitizing effects.
Paclitaxel is a primary chemotherapy agent that displays antitumor activity against a variety of solid tumors. However, the clinical effectiveness of the drug is hampered by its nephrotoxic and ...cardiotoxic side effects. Thus, this investigation aimed at assessing the protective effects of rutin, hesperidin, and their combination to alleviate nephrotoxicity caused by paclitaxel (Taxol), cardiotoxicity in male Wistar rats, as well as oxidative stress. Rutin (10 mg/kg body weight), hesperidin (10 mg/kg body weight), and their mixture were given orally every other day for six weeks. Rats received intraperitoneal injections of paclitaxel twice weekly, on the second and fifth days of the week, at a dose of 2 mg/kg body weight. In paclitaxel-treated rats, the treatment of rutin and hesperidin decreased the elevated serum levels of creatinine, urea, and uric acid, indicating a recovery of kidney functions. The cardiac dysfunction in paclitaxel-treated rats that got rutin and hesperidin treatment also diminished, as shown by a substantial reduction in elevated CK-MB and LDH activity. Following paclitaxel administration, the severity of the kidney and the heart’s histopathological findings and lesion scores were markedly decreased by rutin and hesperidin administration. Moreover, these treatments significantly reduced renal and cardiac lipid peroxidation while markedly increased GSH content and SOD and GPx activities. Thus, paclitaxel likely induces toxicity in the kidney and the heart by producing oxidative stress. The treatments likely countered renal and cardiac dysfunction and histopathological changes by suppressing oxidative stress and augmenting the antioxidant defenses. Rutin and hesperidin combination was most efficacious in rescuing renal and cardiac function as well as histological integrity in paclitaxel-administered rats.
Paclitaxel, one of the most effective chemotherapeutic drugs, is used to treat various cancers but it is exceedingly toxic when used long-term and can harm the liver. This study aimed to see if ...rutin, hesperidin, and their combination could protect male Wistar rats against paclitaxel (Taxol)-induced hepatotoxicity. Adult male Wistar rats were subdivided into 5 groups (each of six rats). The normal group was orally given the equivalent volume of vehicles for 6 weeks. The paclitaxel-administered control group received intraperitoneal injection of paclitaxel at a dose of 2 mg/Kg body weight twice a week for 6 weeks. Treated paclitaxel-administered groups were given paclitaxel similar to the paclitaxel-administered control group together with oral supplementation of rutin, hesperidin, and their combination at a dose of 10 mg/Kg body weight every other day for 6 weeks. The treatment of paclitaxel-administered rats with rutin and hesperidin significantly reduced paclitaxel-induced increases in serum alanine transaminase, aspartate transaminase, lactate dehydrogenase, alkaline phosphatase, and gamma-glutamyl transferase activities as well as total bilirubin level and liver lipid peroxidation. However, the levels of serum albumin, liver glutathione content, and the activities of liver superoxide dismutase and glutathione peroxidase increased. Furthermore, paclitaxel-induced harmful hepatic histological changes (central vein and portal area blood vessel congestion, fatty changes, and moderate necrotic changes with focal nuclear pyknosis, focal mononuclear infiltration, and Kupffer cell proliferation) were remarkably enhanced by rutin and hesperidin treatments. Moreover, the elevated hepatic proapoptotic mediator (caspase-3) and pro-inflammatory cytokine (tumor necrosis factor-α) expressions were decreased by the three treatments in paclitaxel-administered rats. The cotreatment with rutin and hesperidin was the most effective in restoring the majority of liver function and histological integrity. Therefore, rutin, hesperidin, and their combination may exert hepatic protective effects in paclitaxel-administered rats by improving antioxidant defenses and inhibiting inflammation and apoptosis.
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