B. H. Ali

Agents ameliorating or augmenting experimental gentamicin nephrotoxicity: some recent research

Despite its nephrotoxic potential, the aminoglycoside antibiotic gentamicin (GM) is still considered to be an important agent against life-threatening infections. The goal of reducing or protecting against its nephrotoxicity has attracted much effort and attention during the last decade. This article reviews some of the literature published during the last decade on the effects of agents that ameliorate or augment GM nephrotoxicity. Notable among the ameliorating agents are antioxidant agents. These include different classes of compounds that include beta blockers (e.g. carvedilol), superoxide dismutase mimetic agents (e.g. M40403), hormones (e.g. melatonin), iron chelators (e.g. deferrioxamine), vitamins (vitamin C and E) and medicinal plants (e.g. garlic). Other ameliorating agents include antibiotics (e.g. ceftriaxone), antiplatelet drugs (e.g. trapidil) and Ca++ agents that may augment GM nephrotoxicity include cyclosporin and the Ca++-channel blocker verapamil.

Gastrointestinal transit in mice treated with various extracts of date (Phoenix dactylifera L.).

Dates are commonly consumed, especially in the Middle East, but their effect on gastrointestinal transit (GIT) has not been quantified. The effect of water and ethanol extracts from date flesh and date pits on the GIT in mice was studied. Fasted unanaesthetized male mice received by gavage either the vehicle (0.02 m/kg), or the extracts at doses of 0.01, 0.02 or 0.04 ml/kg. Two separate groups received either clonidine (1 mg/kg) or yohimbine (2 mg/kg). Two hours later, all animals were given a test meal containing charcoal and gum arabic in water. Thirty min thereafter, they were killed and the distance the charcoal column had traveled along the small intestine was measured. Compared with the control, the animals that received the ethanol and water extracts of both date flesh and pits emptied, in a dose-dependent manner, more of their gastrointestinal content. The increase in the GIT ranged from 4 to 22%. However, water extract from dialyzed date flesh induced a dose-dependent decrease in GIT that ranged from 4 to 24%. Clonidine exerted a significant decrease (68%), and yohimbine a significant increase (30%) in the GIT. Depending on the method of extraction, the date extracts may exert an increase or a decrease in GIT.

The Effect of Treatment with Gum Arabic on Gentamicin Nephrotoxicity in Rats: A Preliminary Study

In the present work we assessed the effect of treatment of rats with gum Arabic on acute renal failure induced by gentamicin (GM) nephrotoxicity. Rats were treated with the vehicle (2 mL/kg of distilled water and 5% w/v cellulose, 10 days), gum Arabic (2 mL/kg of a 10% w/v aqueous suspension of gum Arabic powder, orally for 10 days), or gum Arabic concomitantly with GM (80 mg/kg/day intramuscularly, during the last six days of the treatment period). Nephrotoxicity was assessed by measuring the concentrations of creatinine and urea in the plasma and reduced glutathione (GSH) in the kidney cortex, and by light microscopic examination of kidney sections. The results indicated that concomitant treatment with gum Arabic and GM significantly increased creatinine and urea by about 183 and 239%, respectively (compared to 432 and 346%, respectively, in rats treated with cellulose and GM), and decreased that of cortical GSH by 21% (compared to 27% in the cellulose plus GM group) The GM-induced proximal tubular necrosis appeared to be slightly less severe in rats given GM together with gum Arabic than in those given GM and cellulose. It could be inferred that gum Arabic treatment has induced a modest amelioration of some of the histological and biochemical indices of GM nephrotoxicity. Further work is warranted on the effect of the treatments on renal functional aspects in models of chronic renal failure, and on the mechanism(s) involved.

Comparative Plasma Pharmacokinetics and Tolerance of Florfenicol following Intramuscular and Intravenous Administration to Camels, Sheep and Goats

Florfenicol, a monofluorinated analogue of thiamphenicol, has a broad antibacterial spectrum. The pharmacokinetics of florfenicol was studied following a single intravenous (i.v.) or intramuscular (i.m.) injection at a dose of 20 mg/kg body weight in healthy male camels, sheep and goats. The concentration of florfenicol in plasma was determined using a microbiological assay. Pharmacokinetic analysis was performed using a two-compartment open model. Following i.m. administration, the maximum plasma concentration of florfenicol (Cmax) reached in camels, sheep and goats was 0.84±0.08, 1.04±0.10 and 1.21±0.10 μg/ml, respectively, the the time required to reach Cmax (tmax) in the same three respective species was 1.51±0.14, 1.44±0.10 and 1.21±0.10 h. The terminal half-life (t1/2β) and the fraction of the drug absorbed (F%) in camels, sheep and goats were 151.3±16.33, 137.0±12.16 and 127.4±11.0 min, and 69.20%±7.8%, 65.82%±6.7% and 60.88%±5.9%, respectively. The MRT in the same three respective species was 4.01±0.45, 3.42±0.39 and 2.98±0.32 h. Following i.v. administration, the terminal half-life (t1/2β) and total body clearance (ClB) in camels, sheep and goats were 89.5±9.2, 78.8±8.3 and 71.1±8.9 min and 0.33±0.04, 0.30±0.03 and 0.27±0.03 L/h per kg, respectively. The area under the curve (AUC0–∞) and the mean residence time (MRT) in the same three respective species were 60.61±6.98, 62.45±6.56 and 74.07±7.85 μg/ml per h, and 2.71±0.31, 2.34±0.25 and 2.11±0.23 h. These data suggest that sheep and goats absorb and clear florfenicol to a broadly similar extent, but the rate and extent of absorption of the drug tends to be higher in camels. Drug treatment caused no clinically overt adverse effects. Plasma enzyme activities and metabolites indicative of hepatic and renal functions measured 1, 2, 4 and 7 days following the drug treatment were within the normal range, indicating that the drug is safe at the dose used.

Nephroprotective Action of Phoenix dactylifera in Gentamicin-Induced Nephrotoxicity

Abstract We investigated the effect of an extract of the flesh and pits of dates [Phoenix dactylifera. L (Arecaceae or Palmae)] on gentamicin (GM) nephrotoxicity in rats. The animals were given either the date flesh extract mixed with the food (50% w/w) or the pits extract mixed in the drinking water (2:1 w/v), and GM (80 mg kg−1 day−1 intramuscularly for 6 days) was injected during the last 6 days of treatment. Other groups of rats were given GM concomitantly with the date flesh extract or the date pits extract at the above doses. GM treatment significantly increased the plasma concentrations of creatinine and urea and induced a marked necrosis of the renal proximal tubules. The date flesh and pits were effective in significantly reducing the increases in plasma creatinine and urea concentrations induced by GM nephrotoxicity and ameliorating the proximal tubular damage. Antioxidant components in the date (e.g., melatonin, vitamin E, and ascorbic acid) were suggested to be the basis of the nephroprotection.

CENTRAL NERVOUS SYSTEM ACTIVITY OF RHAZYA STRICTA (DECNE) IN MICE

1. The effects of orally administered aqueous lyophilized extract of the leaves of Rhazya stricta (2, 4 & 8 g/kg) on aspects of nervous system function were investigated in mice.

The effect of calcium load and the calcium channel blocker verapamil on gentamicin nephrotoxicity in rats.

Gentamicin (GM) is used against serious and life-threatening Gram negative infections. However its use is limited by the occurrence of nephrotoxicity. Reports on the interaction between GM nephrotoxicity and calcium (Ca(2+)) or Ca blockers are conflicting. Therefore, in the present work we assessed the effect of treatment of rats with graded doses of calcium carbonate, CaCO(3) (0.25, 0.5 or 1.0 g/kg) orally, or the Ca(2+) channel blocker verapamil (1.75, 3.5 or 7.0 mg/ kg) intramuscularly (i.m.), on the nephrotoxicity induced by concomitant i.m. treatment with GM (80 mg /kg/day for 6 days). Nephrotoxicity was evaluated histopathologically by light microscopy and biochemically by measuring the concentrations of urea and creatinine in plasma, reduced glutathione (GSH), lipid peroxidation and superoxide dismutase (SOD) activity in kidney cortex. The results indicated that the administration of CaCO(3) produced a dose-dependent amelioration in the biochemical indices of nephrotoxicity in plasma and renal cortex, which was significant at the two higher doses used. The histological picture of the renal proximal tubules followed a similar pattern. Treatment with verapamil induced a dose-dependent potentiation in the biochemical parameters of nephrotoxicity that was significant only at the highest dose used (7 mg/kg). This dose also exacerbated the GM-induced histological necrosis. The above interactions may be clinically relevant in patients treated concurrently with these agents.

Some effects of Salvia aegyptiaca L. on the central nervous system in mice

Salvia aegyptiaca L. is used for treating various unrelated conditions that include nervous disorders, dizziness, trembling, diarrhoea and piles. This work examines some effects of the crude acetone and methanol extracts of the plant given at single oral doses of 0.25, 0.5, 1 or 2 g/kg, on the central nervous system (CNS) in mice. The extracts were also tested for anti-inflammatory and antipyretic actions. Several models of nociception have been used to examine the analgesic effect of the extract. In treated mice, the extracts caused dose-related inhibition of acetic acid-induced abdominal constriction, and significantly reduced formalin-induced pain. Treatment with the extracts at doses of 0.5 and 1 g/kg significantly increased the reaction time in the hot-plate test. In treated mice both extracts caused significant and dose-related impairment of the sensorimotor control and motor activity. Treatment with both extracts did not significantly affect the rectal temperature of normothermic mice. The methanol extract (0.5 and 1.0 g/kg) did not affect the rectal temperature of hyperthermic mice, but the acetone extract was effective in significantly reducing the rectal temperature of hyperthermic mice, 0.5 and 1 h after administration of the extract at doses of 0.25-2 g/kg. It is concluded that the crude methanol and acetone extracts of S. aegyptiaca have CNS depressant properties, manifested as antinociception and sedation. Both extracts have some anti-inflammatory and antipyretic actions. On the whole, the acetone extract appeared to be slightly more effective than the methanol extract in this regard.

Effect Of Grapefruit Juice On Plasma Chloroquine Kinetics In Mice

1.u2002It is known that grapefruit juice (GFJ) may interact with drugs concomitantly administered by inhibiting first‐pass metabolism during the intestinal absorption phase. However, its interaction with chloroquine has not been studied previously.

Isolation Stress in Desert Sheep and Goats and the Influence of Pretreatment with Xylazine or Sodium betaine

We studied some behavioural, clinical, biochemical and haematological variables in Desert (Najdi) sheep and goats subjected to the acute stressful stimulus of isolation from the flock, and the influence of pretreatment with xylazine (n = 6) or sodium betaine (n = 6). The isolation stress resulted in increased vocalization and in variable and statistically nonsignificant increases in heart, pulse and respiratory rates. Isolation caused significant increases in the plasma concentrations of cortisol (from about 35.2 to about 83.8 mmol/L) and glucose (from 3.1 to 4.2 mmol/L), and a decrease in that of magnesium (from 0.82 to 0.65 mmol/L). The endogenous thiocyanate concentration was unaffected. The isolation stress also significantly decreased the haematocrit (PCV), and the number of lymphocytes, and increased the concentration of haemoglobin. Pretreatment of sheep and goats with xylazine at a dose of 0.01 mg/kg by the intravenous route significantly ameliorated the effects induced by the stressful stimulus. The effects of pretreatment of the two species with sodium betaine (10 mg/kg) produced variable and nonsignificant effects. There were no significant differences between sheep and goats in the responses to the isolation stress, except in vocalization, which was greater in sheep than in goats.