Mohammed Al Za'abi

New model for adenine-induced chronic renal failure in mice, and the effect of gum acacia treatment thereon: Comparison with rats

INTRODUCTION This study aimed at comparing the effects of feeding mice and rats with adenine to induce a state of chronic renal failure (CRF), and to assess the effect of treatment with gum acacia (GA) thereon. METHODS We compared the outcome, in mice, of feeding adenine at three different doses (0.75%, 0.3%, and 0.2%, w/w). Biochemical and histopathological studies were conducted in plasma, urine and renal homogenates from both species. RESULTS When mice and rats were fed adenine (0.75%, w/w), all treated rats survived the treatment, but all treated mice died within 1-2 days. The dosage in mice was reduced to 0.3%, w/w, for 4 weeks, but again all treated mice died within 3-4 days. A further reduction in the dosage in mice to 0.2%, w/w, for 4 weeks resulted in no mortality, and produced alterations similar to those observed in rats fed adenine at a dose of 0.75%,w/w, for 4 weeks. Plasma creatinine, urea and urinary protein were significantly increased (P<0.001) in adenine-treated mice and rats, and this action was incompletely, but significantly (P<0.05), reversed by GA. Adenine significantly (P<0.001) reduced superoxide dismutase (SOD) activity and reduced glutathione (GSH) concentration in renal homogenates from both species, and these reductions were significantly (P<0.05) ameliorated by GA. DISCUSSION Our data suggest that mice are more sensitive to adenine than rats, and that a dose of adenine of 0.2%, w/w, for 4 weeks in mice is suggested as a model for CRF. In both models, GA (15%, w/v, in the drinking water for 4 weeks) given concomitantly with adenine ameliorated the severity of CRF to a similar extent.

HPLC–Fluorescence Method for Measurement of the Uremic Toxin Indoxyl Sulfate in Plasma

A sensitive and reproducible high-performance liquid chromatography-fluorescence method was developed and validated for quantitative determination of indoxyl sulfate in plasma using methyl paraben as an internal standard. The separation was carried out on an OSD-2 C18 Spherisorb column by isocratic elusion with sodium acetate buffer (pH 4.5) and acetonitrile (10:90, v/v) as the mobile phase. The method was validated and found to be linear in the range of 2.5 to 50 µM. The limit of quantification was 2.0 µM. The variations for intra-day and inter-day precision were less than 10.1%, and the accuracy values were between 93.4 and 102.5%. The extraction recoveries were more than 89%.

Analyses of anticancer drugs by capillary electrophoresis: a review

Capillary electrophoresis is a fast, inexpensive and low detection limit technique for the analysis of anticancer drugs. It has been used to analyze various anticancer drugs in biological samples, pharmaceutical preparations and environmental matrices. It has also been used to detect various cancer biomarkers in cancer patients. The present article describes the state-of-the art of capillary electrophoresis for the analyses of anticancer drugs. Various drugs discussed belong to several groups such as antimitotic agents, nucleoside analogs, antibiotics, topoisomerase inhibitors and DNA intercalating agents. In addition, efforts have also been made to discuss sample preparation, applications of capillary electrophoresis in genomic research, optimization and future perspectives.

Therapeutic Effect of Chrysin on Adenine-Induced Chronic Kidney Disease in Rats

Background/Aims: To study the therapeutic effect of chrysin, a flavonoid with strong antioxidant and anti-inflammatory activities, on adenine-induced chronic kidney diseases (CKD) in rats. Methods: Chrysin, in three graded oral doses (10, 50 and 250 mg/kg), was given for 10 consecutive days to rats after the induction of CKD by feeding them adenine (0.25%w/w for 35 days). Several plasma and urine biomarkers and tissues morphology were used the investigate chrysin effect on kidney structure and function. Results: Adenine lowered creatinine clearance and elevated the concentrations of urea, creatinine, plasma neutrophil gelatinase-associated lipocalin and urinary N-Acetyl-beta-D-glucosaminidase activity, and increased the concentrations of the uremic toxin indoxyl sulfate, in addition to some inflammatory cytokines. Renal histopathological markers of inflammation and fibrosis were significantly increased. Renal catalase and superoxide dismutase activities, total antioxidant capacity and reduced glutathione were all adversely affected. Most of these adenine - induced actions were moderately mitigated by chrysin, especially at the highest dose. Compared to control, chrysin did not cause any overt adverse effects on the treated rats. Conclusion: Different doses of chrysin produce variable therapeutic salutary effects in rats with CKD, and that, pending further studies, its usability as a possible therapeutic agent in human CKD should be considered.

Effect of aqueous extract and anthocyanins of calyces of Hibiscus sabdariffa (Malvaceae) in rats with adenine-induced chronic kidney disease

The aim of this work was to assess the possible beneficial effects of aqueous extracts of Hibiscus sabdariffa L. calyces and anthocyanins isolated therefrom in an adenine‐induced chronic kidney disease (CKD) model.

Curcumin Ameliorates Kidney Function and Oxidative Stress in Experimental Chronic Kidney Disease

Chronic kidney disease (CKD) is known to involve inflammation, oxidative stress and apoptosis. Here, we investigated the impact of curcumin (diferuloyl methane, a phenolic turmeric pigment), which has strong antioxidant, anti‐inflammatory and anti‐apoptotic activities on kidney structure and function in rats with adenine‐induced CKD. Rats were treated for 5 weeks with adenine to induce CKD‐like renal damage and combined with three doses of curcumin. Markers of kidney function and oxidative stress were quantified in plasma, urine, renal homogenates and on kidney tissue. Curcumin was found to significantly abate adenine‐induced toxic effects such as reduced creatinine clearance, elevated neutrophil gelatinase‐associated lipocalin levels and raised urinary N‐acetyl‐β‐D‐glucosaminidase activities. Curcumin markedly reduced renal morphological damage and histopathological markers of inflammation, fibrosis and apoptosis. Curcumin further reduced adenine‐induced hypertension, urinary albumin, the inflammatory cytokines IL‐1β, IL‐6 and TNF‐α, cystatin C and adiponectin. It restored plasma sclerostin concentrations and lowered oxidative stress in renal homogenates. In animals treated with the two higher curcumin concentrations, alone or in combination with adenine, an increased expression of the antioxidative transcription factor Nrf2 was found as well as up‐regulation of the activity of its direct target glutathione reductase, and of an indirect target, the glutathione level. In conclusion, curcumin exhibits salutary effects against adenine‐induced CKD in rats by reducing inflammation and oxidative stress via up‐regulation of the transcription factor Nrf2.

Does swimming exercise affect experimental chronic kidney disease in rats treated with gum acacia

Different modes of exercise are reported to be beneficial in subjects with chronic kidney disease (CKD). Similar benefits have also been ascribed to the dietary supplement gum acacia (GA). Using several physiological, biochemical, immunological, and histopathological measurements, we assessed the effect of swimming exercise (SE) on adenine –induced CKD, and tested whether SE would influence the salutary action of GA in rats with CKD. Eight groups of rats were used, the first four of which were fed normal chow for 5 weeks, feed mixed with adenine (0.25% w/w) to induce CKD, GA in the drinking water (15% w/v), or were given adenine plus GA, as above. Another four groups were similarly treated, but were subjected to SE during the experimental period, while the first four groups remained sedentary. The pre-SE program lasted for four days (before the start of the experimental treatments), during which the rats were made to swim for 5 to 10 min, and then gradually extended to 20 min per day. Thereafter, the rats in the 5th, 6th, 7th, and 8th groups started to receive their respective treatments, and were subjected to SE three days a week for 45 min each. Adenine induced the typical signs of CKD as confirmed by histopathology, and the other measurements, and GA significantly ameliorated all these signs. SE did not affect the salutary action of GA on renal histology, but it partially improved some of the above biochemical and physiological analytes, suggesting that addition of this mode of exercise to GA supplementation may improve further the benefits of GA supplementation.

The effect of thymoquinone treatment on the combined renal and pulmonary toxicity of cisplatin and diesel exhaust particles

Particulate air pollution (PAP) exposure is associated with increased morbidity and mortality, particularly in patients with renal disease. However, there are only a few studies on the interaction between PAP and renal injury, and none on agents that may ameliorate it. We studied the interaction between cisplatin (CP) nephrotoxicity and a single exposure to diesel exhaust particle (DEP) in rats 24 h before sacrifice, and assessed the effect of co-treatment with the active ingredient in Nigella Sativa seed oil, thymoquinone (TQ) thereon. Rats were injected intraperitoneally with CP (6 mg/kg) and four days later, they were exposed intratracheally to DEP (0.5 mg/kg), and were sacrificed 24 h later. Oral TQ (20 mg/kg) was given daily throughout the experimental period. CP alone caused several physiological, biochemical, and histopathological changes that included reduced growth and creatinine clearance, and raised plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin 6 (IL-6) and C-reactive protein (CRP), creatinine and urea concentrations, and urinary N-acetyl-b-D-glucosaminidase (NAG) activities. It adversely affected several indices of oxidative damage in the kidneys, and induced renal tubular necrosis. Most of these actions were significantly potentiated in rats given both CP and DEP. TQ significantly abrogated many of the effects of CP and DEP, given alone and in combination. These results provide experimental evidence that subjects with renal diseases can be at higher risk from PAP, and that TQ, pending further pharmacological and toxicological studies, can be considered a useful agent in patients with renal diseases and exposed to PAP.

Renoprotective effects of gamma-aminobutyric acid on cisplatin-induced acute renal injury in rats.

To investigate the effect of gamma‐aminobutyric acid (GABA) on acute renal injury (ARI), we used here a rat model of acute tubular necrosis induced by the anticancer drug cisplatin (CP). GABA was given orally (100 or 500 mg/kg/day for ten consecutive days), and on the 6th day, some of the treated rats were also injected intraperitoneally with either saline or CP (6 mg/kg). Four days after CP treatment, urine was collected from all rats, which were then anaesthetized for blood pressure and renal blood flow monitoring. This was followed by intravenous injection of norepinephrine for the assessment of renal vasoconstrictor responses. Thereafter, blood and kidneys were collected for measurement of several functional, biochemical and structural parameters. GABA treatment (at 500 but not 100 mg/kg) significantly mitigated all the measured physiological and biochemical indices. Sections from saline‐ and GABA‐treated rats showed apparently normal proximal tubules. However, kidneys of CP‐treated rats had a moderate degree of necrosis. This was markedly lessened when CP was given simultaneously with GABA (500 mg/kg). The concentration of platinum in the cortical tissues was not significantly altered by GABA treatment. The results suggested that GABA can ameliorate CP nephrotoxicity in rats. Pending further pharmacological and toxicological studies, GABA may be considered a potentially useful nephroprotective agent in CP‐induced ARI.

Utilization patterns of antiepileptic drugs among adult epileptic patients at a tertiary hospital in Oman.

To describe utilization patterns of antiepileptic drugs (AEDs) among adult epileptic patients at a tertiary hospital in Oman.