Ameliorative effect of sesamin in cisplatin-induced nephrotoxicity in rats by suppressing inflammation, oxidative/nitrosative stress, and cellular damage.

Nephrotoxicity of cisplatin (CP) involves renal oxidative stress and inflammation, and sesamin (a major liganin in many plants) has strong antioxidant and antiinflammatory actions. Therefore, we investigated here the possible mitigative action of sesamin on CP nephrotoxicity in rats. Sesamin was given orally (5 mg/kg/day, 10 days), and on the 7th day, some of the treated rats were injected intraperitoneally with either saline or CP (5 mg/kg). On the 11th day, rats were sacrificed, and blood and urine samples and kidneys were collected for biochemical estimation of several traditional and novel indices of renal damage in plasma and urine, several oxidative and nitrosative indices in kidneys, and assessment of histopathological renal damage. CP significantly and adversely altered all the physiological, biochemical and histopathological indices of renal function measured. Kidneys of CP-treated rats had a moderate degree of necrosis. This was markedly lessened when CP was given simultaneously with sesamin. Sesamin treatment did not significantly alter the renal CP concentration. The results suggested that sesamin had ameliorated CP nephrotoxicity in rats by reversing the CP-induced oxidative stress and inflammation. Pending further pharmacological and toxicological studies sesamin may be considered a potentially useful nephroprotective agent.

Anemia in adenine-induced chronic renal failure and the influence of treatment with gum acacia thereon.

Anemia frequently complicates chronic kidney disease (CKD). We investigated here the effect of adenine-induced CKD in rats on erythrocyte count (EC), hematocrit (PCV) and hemoglobin (Hb) concentration, as well as on the activity of L-gamma-glutamyl transferase (GGT) and the concentrations of iron (Fe), transferrin (Tf), ferritin (F), total iron binding capacity (TIBC) / unsaturated iron binding capacity (UIBC) and hepcidin (Hp) in serum and erythropoietin (Epo) in renal tissue. Renal damage was assessed histopathologically, and also by measuring the serum concentrations of the uremic toxin indoxyl sulfate (IS), creatinine, and urea, and by creatinine clearance. We also assessed the influence of concomitant treatment with gum acacia (GA) on the above analytes. Adenine feeding induced CKD, accompanied by significant decreases (P<0.05) in EC, PCV, and Hb, and in the serum concentrations of Fe, Tf, TIBC, UIBC and Epo. It also increased Hp and F levels. GA significantly ameliorated these changes in rats with CKD. A general improvement in the renal status of rats with CKD after GA is shown due to its anti-inflammatory and anti-oxidant actions, and reduction of the uremic toxin IS, which is known to suppress Epo production, and this may be a reason for its ameliorative actions on the indices of anemia studied.

Antimicrobial agent prescription patterns for chemotherapy-induced febrile neutropenia in patients with hematological malignancies at Sultan Qaboos University Hospital, Oman.

OBJECTIVES: The aim of this study was to describe the antimicrobial prescription patterns of patients with hematological malignancies who developed febrile neutropenia (FN) at Sultan Qaboos University Hospital (SQUH) in Oman. METHODS: This was a retrospective observational study covering a period of 3 years (January 2007-February 2010). FN episodes were studied in patients with hematological malignancies in three different wards at SQUH. RESULTS: A total of 176 FN episodes were analyzed. Overall, 64% of the 107 patients studied experienced at least 2 episodes during the analysis period. Approximately, 69% of the febrile neutropenia episodes had severe neutropenia. The duration of neutropenia was less than 1 week in the majority of the episodes (57%). The mean duration of treatment was approximately 7 days, with no significant difference between specialties or different types of malignancies. Only 34 (19%) episodes had positive cultures, and most of these were from blood samples (30 episodes, 88%). The majority of isolates were gram-negative organisms (63%). The initial empirical treatment included monotherapy (37%), dual therapy (60%) and triple therapy (3%). CONCLUSIONS: This study demonstrates that there is a large variation in the antimicrobial treatment of FN episodes in patients with hematological malignancies at SQUH. All chosen drugs were within international guideline recommendations.

Comparative protective effect of N-acetyl cysteine and tetramethylpyrazine in rats with gentamicin nephrotoxicity.

Gentamicin (GM) is used against serious and life-threatening infections, but its use is limited by the occurrence of nephrotoxicity, which involves the generation of free radicals. In this work we tested the effect of a compound with antioxidant properties, tertamethylpyrazine (TMP), a major constituent of the Chinese medicinal plant Lingusticum wallichi, on GM-induced nephrotoxicity, and compared it with an established anti-oxidant compound N-acetyl cysteine (NAC). Six groups of rats were studied: (1) control, treated orally (p.o.) and intraperitoneally (i.p.) with saline; (2) treated i.p. with GM (80 mg kg(-1) per day for 6 days); (3) TMP, given p.o. (100 mg kg(-1) per day for 10 days) + GM (same dose as above during the last 6 days); (4) NAC, given i.p. (500 mg kg(-1) per day for 10 days) + GM as above; (5) TMP (100 mg kg(-1) per day for 10 days) + saline; (6) NAC (500 mg kg(-1) per day for 10 days) + saline. GM nephrotoxicity was characterized by reduced creatinine clearance, increased creatinine and urea concentrations in plasma, increased urinary excretion of N-acetyl-beta-d-glucosaminidase (NAG) and total protein. These functional and structural alterations were prevented or ameliorated by NAC treatment, while TMP had only a slight mitigating effect that was less marked than that produced by NAC. The concentration of GM in the renal cortex of the rats given GM + NAC (but not TMP) was lower than that found in rats treated with GM alone by about 25%. The mechanism by which NAC and, to a lesser extent TMP, protected against GM-induced nephrotoxicity may be related, at least in part, to the decrease in oxidative stress in renal cortex.

Amelioration of cisplatin-induced nephrotoxicity in rats by tetramethylpyrazine, a major constituent of the Chinese herb Ligusticum wallichi.

Nephrotoxicity of the anticancer drug, cisplatin (CP) involves enhanced renal generation of reactive oxygen metabolites and lipid peroxidation caused by decreased levels of antioxidants and antioxidant enzymes. Tetramethylpyrazine (TMP) is known to act as a strong antioxidant. Therefore, in the present work, we aimed at testing the possible protective or palliative effect of TMP on CP nephrotoxicity in rats. TMP was given orally at a dose of 80 mg . kg(- 1) . day(- 1) for 7 days. Some of these rats were given a single intraperitoneal injection of CP (or vehicle) at a dose of 6 mg/kg on Day 6 of treatment. Animals were sacrificed 6 days after CP (or vehicle) treatment, and blood, urine, and kidneys were obtained. Nephrotoxicity was assessed biochemically by measuring creatinine and urea in serum, reduced glutathione (GSH) concentration in renal cortex, by urinalysis, and histopathologically by light microscopy. CP significantly increased the concentration of urea and creatinine (P < 0.05) by about 128% and 170%, respectively; increased urine volume and N-acetyl-beta-D-glucosaminidase (NAG) activity; and significantly decreased osmolality and protein concentrations. CP treatment reduced GSH by about 34% (P < 0.05) and superoxide dismutase (SOD) and total antioxidant activity (TOX) by about 28% and 21%, respectively (P < 0.05). TMP pretreatment significantly mitigated all of these effects. Sections from saline- and TMP-treated rats showed apparently normal proximal tubules. However, kidneys of CP-treated rats had a moderate degree of necrosis. This was markedly reduced when CP was given after pretreatment with TMP. CP cortical concentration was not significantly altered by TMP treatment. The results suggest that TMP ameliorated the histological, physiological, and biochemical indices of nephrotoxicity in rats. Pending further pharmacological and toxicological studies, TMP may potentially be useful as a nephroprotective agent.

The ameliorative effect of dates (Phoenix dactylifera L.) on ethanol-induced gastric ulcer in rats.

The present work aimed at testing, in a rat model of ethanol-induced gastric ulceration, a local folk medicinal claim that dates are beneficial in gastric ulcers in humans. Aqueous and ethanolic undialyzed and dialyzed extracts from date fruit and pits were given orally to rats at a dose of 4 ml/kg for 14 consecutive days. On the last day of treatment, rats were fasted for 24 h, and were then given ethanol, 80% (1 ml/rat) by gastric intubation to induce gastric ulcer. Rats were killed after 1 h of ethanol exposure, and the incidence and severity of the ulceration were estimated, as well as the concentrations of gastrin in plasma, and histamine and mucus in the gastric mucosa. A single group of rats that were fasted for 24 h, was administered orally with lansoprazole (30 mg/kg), and was given 80% ethanol as above, 8 h thereafter, served as a positive control. The results indicated that the aqueous and ethanolic extracts of the date fruit and, to a lesser extent, date pits, were effective in ameliorating the severity of gastric ulceration and mitigating the ethanol-induced increase in histamine and gastrin concentrations, and the decrease in mucin gastric levels. The ethanolic undialyzed extract was more effective than the rest of the other extracts used. It is postulated that the basis of the gastroprotective action of date extracts may be multi-factorial, and may include an anti-oxidant action.

The effect of Nigella sativa oil on gentamicin nephrotoxicity in rats.

The pathogenesis of gentamicin (GM) nephrotoxicity has been shown to involve the generation of oxygen free radicals, and several free radical scavengers have been shown to ameliorate the nephrotoxicity. The seeds and oil of Nigella sativa are reported to possess strong antioxidant properties and was effective against disease and chemically-induced hepatotoxicity and nephrotoxicity. Therefore, in the present work, we have tested whether oral treatment of rats with N. sativa oil (0.5, 1.0 or 2.0 ml/kg/day for 10 days) would ameliorate nephrotoxicity of GM (80 mg/kg/day given intramuscularly and concomitantly with the oil during the last 6 days of treatment). Nephrotoxicity was evaluated histopathologically with a light microscope and by measurement of concentrations of urea, creatinine and total antioxidant status (TAS) in plasma and reduced glutathione (GSH) and TAS in kidney cortex. The results indicated that GM treatment caused moderate proximal tubular damage, significantly increased the concentrations of creatinine and urea, and decreased that of TAS and GSH. Treatment with N. sativa oil produced a dose-dependent amelioration of the biochemical and histological indices of GM nephrotoxicity that was statistically significant at the two higher doses used. Compared to controls, treatments of rats with N. sativa did not cause any overt toxicity, and it increased GSH and TAS concentrations in renal cortex and enhanced growth. The results suggest that N. sativa may be useful in ameliorating signs of GM nephrotoxicity in rats, and pending further experimentation to determine safety and efficacy, may be useful clinically.

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.

The effect of a strongly basic alkaloidal fraction of Rhazya stricta, a traditional medicinal plant, on cytochrome P450-mediated metabolism of theophylline in mice.

The strongly basic alkaloidal fraction of the traditional medicinal plant Rhazya stricta (RS) was given orally to mice, in a single dose of 10 mg/kg (group 1) or, twice daily for 3 days at the same dose (group 2). A third group (control) received normal saline. Liver homogenates from all animals were used to assess the microsomal activity of cytochrome P450 and its isoforms as well as its catalytic activity (using theophylline as a substrate). RS alkaloidal fraction had no significant effect on the total amount of microsomal cytochrome P450, but it caused a significant increase in the cytochrome P450 isoforms CYPs 1A1 and 1A2. It also significantly increased the concentrations of some metabolites of theophylline. These results suggest that RS has the potential to interact with other drugs that are biotransformed by cytochrome P450, when given concomitantly with it.

Pharmacological and toxicological properties of Nigella sativa.

The seeds of Nigella sativa Linn. (Ranunculaceae), commonly known as black seed or black cumin, are used in folk (herbal) medicine all over the world for the treatment and prevention of a number of diseases and conditions that include asthma, diarrhoea and dyslipidaemia. This article reviews the main reports of the pharmacological and toxicological properties of N. sativa and its constituents. The seeds contain both fixed and essential oils, proteins, alkaloids and saponin. Much of the biological activity of the seeds has been shown to be due to thymoquinone, the major component of the essential oil, but which is also present in the fi ed oil. The pharmacological actions of the crude extracts of the seeds (and some of its active constituents, e.g. volatile oil and thymoquinone) that have been reported include protection against nephrotoxicity and hepatotoxicity induced by either disease or chemicals. The seeds/oil have antiinflammatory, analgesic, antipyretic, antimicrobial and antineoplastic activity. The oil decreases blood pressure and increases respiration. Treatment of rats with the seed extract for up to 12 weeks has been reported to induce changes in the haemogram that include an increase in both the packed cell volume (PCV) and haemoglobin (Hb), and a decrease in plasma concentrations of cholesterol, triglycerides and glucose. The seeds are characterized by a very low degree of toxicity. Two cases of contact dermatitis in two individuals have been reported following topical use. Administration of either the seed extract or its oil has been shown not to induce significant adverse effects on liver or kidney functions. It would appear that the beneficial effects of the use of the seeds and thymoquinone might be related to their cytoprotective and antioxidant actions, and to their effect on some mediators of inflammation.

The effect of a water extract and anthocyanins of hibiscus sabdariffa L on paracetamol-induced hepatoxicity in rats.

We investigated the effect of the water extract of the dried flowers of Hibiscus sabdariffa L. and Hibiscus anthocyanins (HAs) (which are a group of natural pigments occurring in the dried calyx of H. sabdariffa) on paracetamol-induced hepatotoxicity in rats. The water extract was given in lieu of drinking water for 2, 3 or 4 consecutive weeks, and the HAs were given orally at doses of 50, 100 and 200 mg/Kg for five consecutive days. Paracetamol was given orally at a dose of 700 mg/Kg to induce hepatotoxicity at the end of the water extract and Has treatments. Six hours thereafter the rats were killed and their liver function evaluated biochemically and histologically. Given for 4 weeks (but not for 2 or 3 weeks) the extract significantly improved some of the liver function tests evaluated, but did not alter the histology of the paracetamol-treated rats or the pentobarbitone-induced sleeping time. At a dose of 200 mg/Kg, the hepatic histology and the biochemical indices of liver damage were restored to normal. Lower does were ineffective. Pending more evaluation for safety and efficacy, the HAs can potentially be used in mitigating paracetamol-induced hepatotoxicity.

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.

Central nervous system activity of Leucas inflata Benth. in mice.

The analgesic activity of the methanol and acetone extracts of Leucas inflata L. (family Labiatae) was evaluated in mice using different experimental models. The effect of the two extracts on pentobarbitone-sleeping time, motor activity, sensorimotor coordination, carrageen induced inflammation, and brewer's yeast-induced pyrexia has also been investigated. The two crude extracts have been phytochemically analyzed and some constituents isolated and characterized. These included stigmasterols, a chromone and coumarins. Extracts of L. inflata L., given at single oral doses of 0.25, 0.5, 1.0 or 2.0 g/kg, significantly and dose-dependently, reduced formalin-induced pain, acetic acid induced abdominal constrictions and increased the reaction time in the hot-plate test. Both extracts caused significant and dose-related impairment in the sensorimotor control and ambulatory and total motor activity of treated mice. Both extracts exhibited anti-inflammatory action by reducing paw edema of treated mice. The extracts did not significantly affect the rectal temperature of normothermic mice. However, they were effective in preventing Brewers yeast induced pyrexia. It is concluded that the crude methanol and acetone extract of L. inflata has CNS depressant properties, manifested as antinociception and sedation. Both extracts have anti-inflammatory and antipyretic actions.

Liquorice (Glycyrrhiza glabra) and the adrenal-kidney-pituitary axis in rats.

The effect of oral administration of a water freeze-dried extract of Glycyrrhiza glabra (liquorice) has been studied at doses of 100, 250 and 500 mg/kg in rats on the plasma concentration of cortisol, adrenocorticotrophic hormone (ACTH), aldosterone, renin, sodium (Na) and potassium (K). The results indicated that treatment induced dose-dependent and mostly significant decreases in the concentration of cortisol, ACTH, aldosterone and K. There were concomitant dose-dependent increases in the concentrations of renin and Na. The results suggest a strong and dose-dependent suppression of the adrenal-pituitary axis, accompanied by stimulation of renin production from the kidney.

The effect of treatment with the medicinal plant Rhazya stricta decne on gentamicin nephrotoxicity in rats.

Generation of oxygen free radicals in kidney cortex plays an important role in the pathogenesis of gentamicin (GM) nephrotoxicity, and the leaf extract of the medicinal plant Rhazya stricta has been shown to have an anti-oxidant action in rats. Therefore, in the present work we aimed at testing, in this species, the possible protective effect of R. stricta extract on GM nephrotoxicity. Crude water extract of R. Stricta leaves (0.25, 0.5 and 1 g/Kg) was given orally to rats four days before GM treatment, and thereafter, concomitantly with GM (80 mg/Kg/day) for another six days. Nephrotoxicity was evaluated histopathologically by light microscopy, and biochemically by measuring the concentrations of urea and creatinine in serum, reduced glutathione (GSH), lipid peroxidation and superoxide dismutase (SOD) activity in kidney cortex. The results suggested that the plant extract (0.25 g/Kg) was ineffective in significantly altering the indices of GM-induced nephrotoxicity. However, a dose-related amelioration in the indices of toxicity was noted when the two higher doses of the plant extract were given. The plant extract, at the three doses used, had no significant adverse effect on the body weight of treated rats or on the measured hepatic and renal functions in serum. However, the two higher doses, significantly and dose-dependently increased SOD activity and GSH concentration, and decreased that of lipid peroxides in the kidney cortex. These results suggest that R. stricta water extract may contain compounds that could potentially ameliorate GM nephrotoxicity in rats.

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 the traditional medicinal plants Rhazya stricta, Balanitis aegyptiaca and Haplophylum tuberculatum on paracetamol-induced hepatotoxicity in mice.

This work examines the effects of lyophilized extracts of the medicinal plants Rhazya stricta, Balanites aegyptiaca and Haplophylum tuberculatum on liver damage induced by paracetamol in mice. Rapid HPLC finger prints for some of these extracts were made. The hepatoprotective effects of the plant extracts were compared with that of the standard hepatoprotective agent silymarin. The extracts (1 g/kg) and silymarin (0.1 g/kg) were given orally for 5 consecutive days. On the last day of treatment a hepatotoxic oral dose of paracetamol (0.6 g/kg) was given, and 3 h later, the hepatic function of mice was evaluated using pentobarbitone -induced sleeping time, the concentration of reduced glutathione (GSH) in liver, and the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and cholesterol concentration in plasma. The livers were weighed and examined for macro- and microscopic changes. Pretreatment with R. stricta or with silymarin protected the livers of treated mice against paracetamol hepatotoxicity as evidenced by a significant improvement of the above liver function tests. B. Aegyptiaca had a relatively modest hepatoprotective activity, while H. tuberculatum was almost ineffective. Oral pretreatment of mice for 5 consecutive days with an extract of R. stricta or silymarin protected about 57% and 92% of the treated mice, respectively, against the lethal effect of paracetamol (1 g/kg). B. aegyptiaca and H. tuberculatum protected only 27% and 16% of the animals, respectively.

Effect of Rhazya stricta Decne on monoamine oxidase and cholinesterase activity and brain biogenic amine levels in rats.

The effect of treatment with the medicinal plant Rhayva stricta Decne, on monoamine oxidase (MAO) and cholinesterase activity, and on the concentration of brain biogenic amines was studied in rats. R. stricta extract, at doses of 0.2 and 0.5 g kg(-1), significantly (P < 0.05-0.01) increased the hepatic and cerebral activity of MAO by 36-127%. The higher doses used (2.0 and 8.0 g kg(-1)) produced smaller (10-26%) and statistically insignificant increases in MAO activity in liver and brain. Cholinesterase activity in blood, liver and brain was not significantly influenced by treatment with R. stricta. The concentrations of the measured biogenic amines (noradrenaline, adrenaline, 5-hydroxytryptamine and dopamine) were significantly lowered in rats treated with R. stricta. The observed increase in MAO activity may be responsible for the lowered biogenic amines levels and may, in part, be responsible for the pharmacological effects of R. stricta extract in rats.

Antioxidant action of extract of the traditional medicinal plant Rhazya stricta Decne. in rats.

The effects of a leaf extract of the traditional medicinal plant Rhazya stricta (0.25, 1.0 and 4.0 g/kg/day for 3 days) on reduced glutathione (GSH), lipid peroxidation (LP) and ascorbic acid (AA) concentrations in the liver and kidneys were studied in rats 24 h after the last dose. The plant extract, at a dose of 0.25 g/kg, did not significantly affect the concentrations of GSH, LP or AA in the liver or kidneys. At a dose of 1.0 g/kg, the plant extract significantly increased the GSH concentration in the liver, but did not affect the GSH concentration in the kidneys, or LP or AA in the liver or kidneys. The plant extract (4.0 g/kg) significantly increased the GSH and decreased LP peroxidation, but did not affect the AA concentrations in the liver and kidneys. It may be concluded that the R. stricta extract, at some of the doses used, has antioxidant actions in the rat.

Thiamin status in furosemide-treated rats.

Rats were treated with furosemide at intraperitoneal doses of 10, 20, and 30 mg kg(-1)day(-1)for 21 days, and some indices of thiamin status (liver, blood and urine thiamin concentrations, erythrocyte transketolase (TK) activity, and thiamin pyrophosphate (TPP) effect, which refers to the increase in TK activity in a deficient haemolysate due to the addition of TPP before incubation) were measured. The results indicated that, at doses of 20 and 30 mg kg(-1)(but not 10 mg kg(-1)), furosemide produced significant effects on these indices suggestive of thiamin deficiency. In another experiment, the effect of thiamin treatment (20 and 100 microg kg(-1)) in rats concomitantly given furosemide (30 mg kg(-1)) was investigated. The high dose of the vitamin was sufficient to overcome the biochemical signs of thiamin deficiency induced by furosemide.