Antioxidant protecting effects of vitamin B6 at reducing hemodynamic toxicity of gentamicin in rat model of nephrotoxicity

Routine therapeutic use of gentamicin in patients with preexisting renal failure may confront us with the toxic effects of aminoglycosides in the kidney known as nephrotoxicity. It is a common and often overlooked clinical entity that presents itself in the setting of oxidative stress-associated diseases in older individuals with renal failure. In this study, we investigated the antioxidant protecting effects of vitamin B₆ in the kidney, with a view on vasoregulatory role of renal pyridoxal 5′-phosphate at reducing the hemodynamic toxicity of gentamicin. Hence, 50 male Sprague–Dawley rats were randomly assigned in five groups to receive a corresponding dose of either normal saline, vitamin B₆ (100 mg/kg/bw; i.m.) or gentamicin alone (80 mg/kg/bw; i.m.), or in combination with vitamin B₆ at low (100 mg/kg/bw; i.m.) and high dose (200 mg/kg/bw; i.m.) for 10 days as animal model of nephrotoxicity. Daily administration of gentamicin at a dose of 80 mg/kg resulted in a significant increase in local and systemic oxidative stress and a decrease in glomerular functions as result of early hemodynamic toxicity. Histopathological examinations of renal tissues revealed acute tubular necrosis with hyaline cast formation triggered by gentamicin over 9 days of the experiment, in addition to interstitial nephritis and tubular epithelial loss. Further biochemical studies in HVB group showed the protecting effects of supplemented vitamin B₆ at a high dose, including a slowdown in urinary enzyme activity, a significant decrease in plasma lipid peroxidation, and an increased tissue superoxide dismutase activity with recovery in the glomerular hemodynamicity and ATPase activity up to 50 % when compared to low-dose rats and controls. In high-dose animals, normal glomerular and tubular function on recovery from toxic renal failure led us to conclude that antioxidant properties of vitamin B₆ consistently increase with dose intensity. The present study also provided evidence that high dose of vitamin B₆ prevented both functional and histological renal changes induced by gentamicin in rats, more efficient than low dose of the vitamin.     

Dose-related protecting effects of vitamin C in gentamicin-induced rat nephrotoxicity: a histopathologic and biochemical study

Gentamicin remains the mainstay in treatment of gram-negative infections, despite its potential ototoxicity and nephrotoxicity. In this study, we investigated dose-related protecting effects of vitamin C against gentamicin-induced rat nephrotoxicity. Hence, 50 male albino Wistar rats were randomly divided into five equal groups to receive a corresponding dose of either normal saline as control, vitamin C (200 mg/kg/bw, i.m.) or gentamicin alone (80 mg/kg/bw, i.m.) or in combination with vitamin C at low dose (200 mg/kg/bw, i.m.; LVG) and high dose (600 mg/kg/bw, i.m.) for 9 days. Daily administration of gentamicin at a dose of 80 mg/kg resulted in a significant increase in oxidative stress in renal tissues and plasma and a concomitant decrease in the creatinine clearance and renal blood flow as result of early hemodynamic toxicity. Histopathological examinations revealed acute tubular necrosis with hyaline cast formation triggered by gentamicin over 9 days of experiment, in addition to interstitial nephritis and tubular epithelial loss. Further biochemical studies showed protecting effects of supplemented vitamin C at a high dose, including slowdown in the urinary enzyme activity, a significant decrease in plasma lipid peroxidation, and an increased tissue superoxide dismutase activity with recovery in the glomerular hemodynamicity and the ATPase activity up to 50% when compared to controls and low-dose rats (LVG). In high-dose animals, normal glomerular and tubular function on recovery from toxic renal failure led us to conclude that antioxidant properties of vitamin C consistently increase with dose intensity. The present study also provided evidence that high dose of vitamin C prevented both functional and histological renal changes induced by gentamicin in rats, more efficient than low dose of the vitamin.     

Vitamin C dose-dependently ameliorates renal hemodynamic toxicity of cisplatin in adult Swiss albino rats: a histopathologic and biochemical study

Nephrotoxicity is usually thought of as a common invariable consequence of hemodynamic toxicity whose effects, including oliguria and dysuria, has largely limited the clinical use of cisplatin. In this study, we investigated the protective effects of low and high dose of vitamin C against cisplatin-induced rat nephrotoxicity. Hence, 50 adult male Swiss albino rats were randomly divided into five equal groups to receive a corresponding dose of either normal saline as control, vitamin C (600 mg/kg/BW, i.v.), or cisplatin alone (7 mg/kg/BW, i.p.) or in combination with vitamin C at low dose (200 mg/kg/BW, i.v.) and high dose (600 mg/kg/BW, i.v.) for 9 days. Daily administration of cisplatin at a dose of 7 mg/kg/BW resulted in a significant increase in oxidative stress in renal tissues and plasma and a concomitant decrease in the creatinine clearance and renal blood flow as a result of early hemodynamic toxicity. Histopathological examination revealed acute tubular necrosis with hyaline cast formation triggered by cisplatin over 9 days of experiment. Further biochemical studies showed protecting effects of supplemented vitamin C at a high dose, illustrated by slowdown in the urinary enzyme activity, a significant decrease in plasma lipid peroxidation, and an increased tissue superoxide dismutase activity with recovery in the glomerular hemodynamicity and the ATPase activity up to 50 % when compared to controls and rats receiving low-dose. In high-dose animals, normal glomerular and tubular function on recovery from toxic renal failure led us to conclude that antioxidant property of vitamin C increases with dose, and, therefore, high dose of vitamin C prevents both functional and histological renal changes induced by cisplatin in rats, more efficient than low dose of the vitamin.     

Carvedilol exacerbate gentamicin-induced kidney mitochondrial alterations in adult rat

Gentamicin is an aminoglycoside antibiotic widely used to treat many types of bacterial infections. Although its properties, his clinical use is limited due to the occurrence of nephrotoxicity, which has been related to mitochondrial dysfunction. Carvedilol, an antihypertensive drug with strong antioxidant properties, has been tested in order to prevent gentamicin nephrotoxicity. This study aimed to test this hypothesis using a rat model of gentamicin-induced nephrotoxicity. Animals were treated subcutaneously with DMSO (control) (0.4%/kg/24 h bw) for 11 days; with carvedilol (2 mg/kg/24 h bw) for 11 days; with gentamicin (60 mg/kg/24 h bw) for the last 8 days and with carvedilol (2 mg/kg/24 h bw) for 11 days and with gentamicin (60 mg/kg/24 h bw) for the last 8 days. Estimations of urine creatinine, urine carboxylic acids, blood urea, serum creatinine and glomerular filtration rate were carried out after the last administered dose of gentamicin. Mitochondria functionality was analyzed by monitoring its bioenergetics function and cardiolipin oxidized products were analyzed by ESI–MS. The kidneys were also examined for morphological changes. Gentamicin caused marked nephrotoxicity and mitochondrial dysfunction as evidenced by several mitochondrial parameters. Carvedilol did not induce significant changes while the co-treatment exacerbated the negative effect of gentamicin although maintaining ATP levels and membrane potential. Kidneys from gentamicin treated rats, with and without carvedilol, showed necrosis of tubular cells in renal cortex. Higher values on relative abundance of cardiolipin oxidation products identified as [M-2H]^2? ions, at m/z 771 were observed in the groups treated with gentamicin. The observed effects were associated to a possible interaction of carvedilol with F₁F₀-ATP synthase that merit further investigation. In conclusion, carvedilol may contribute to the exacerbation of renal dysfunction induced by gentamicin, at least in some physiological and biochemical parameters. From a clinical perspective, and until further conclusions, cautious use of both drugs in combination is advised with particular emphasis in patients presenting mitochondrial disorders.     

Determination of effective dose combination of Azadirachta indica leaf extracts and diminazene diaceturate in the treatment of experimental Trypanosoma brucei brucei infection in rats

This study investigated the effective dose of methanolic Azadirachta indica leaf extracts, MAILE, combined with diminazene diaceturate, DDA, in the treatment of experimental Trypanosoma brucei brucei infection in rats. Acute toxicity study of the drug and extract combinations was carried in non-infected rats. Eleven different groups of ten rats each were used. Ten out of the eleven groups were infected with T. brucei brucei and used to determine the effective dose of MAILE and DDA combination to be used in the treatment of the infection. All the infected rats were treated, viz, 7.0 mg/kg body weight (bw) DDA plus 500 mg/kg bw MAILE (group 1); 7.0 mg/kg body bw DDA plus 250 mg/kg bw MAILE (group 2); 7.0 mg/kg body bw DDA plus 125 mg/kg bw MAILE (group 3); 3.5 mg/kg body bw DDA plus 500 mg/kg bw MAILE (group 4); 3.5 mg/kg body bw DDA plus 250 mg/kg bw MAILE (group 5); 3.5 mg/kg body bw DDA plus 125 mg/kg bw MAILE (group 6); 1.8 mg/kg bw DDA plus 500 mg/kg bw MAILE (group 7); 1.8 mg/kg bw DDA plus 250 mg/kg bw MAILE (group 8); 1.8 mg/kg body bw DDA plus 125 mg/kg bw MAILE (group 9). Two other groups, infected untreated (group 10) and uninfected untreated (group 11), served as negative and positive control, respectively. The parameters assessed to determine the effective dose combination of the two were onset of parasitaemia (OP), level of parasitaemia (LOP), clearance of parasites post-treatment (COPPT), relapse of infection period (RIP), erythrocyte counts (EC), packed cell volume (PCV) and total leucocyte counts (TLC). There was no significant difference (p?<?0.05) in OP between the groups. A day following treatment, the LOP of groups 1, 2, 3 and 4 was found to be significantly lower (p?<?0.05) than that of groups 5 and 6 (p?<?0.05) which in turn was lower (p?<?0.05) than that of groups 7, 8 and 9, respectively. The mean COPPT of groups 5 and 6 was significantly (p?<?0.05) longer than that of groups 1, 2, 3 and 4. There was no significant difference (p?<?0.05) in the mean COPPT among groups 1, 2, 3 and 4. There was no clearance of parasites in groups 7, 8 and 9. The mean RIP of group 5 and 6 was significantly shorter (p?<?0.05) than in group 4. There was no relapse of infection in group 1, 2 and 3 rats. Rats in groups 1, 2, 3 and 4 had significantly higher (p?<?0.05) PCV, EC and TLC 10 days post-treatment, and that trend continued throughout the experimental period when compared to other infected groups. It was concluded that dose combination of 125 mg/kg bw extract plus 7 mg/kg bw DDA was the best dose combination judging from the parameters assessed.     

Comparative efficacy of graded doses of diaminazine aceturate and fixed doses of iron dextran and vitamin B complex in mice infected with <Emphasis Type="Italic">Trypanosoma brucei brucei</Emphasis>

Trypanosomosis is a disease of both domestic animals and man. Trypanosomosis continues to be a menace in the livestock industry in Nigeria despite the agelong attempt to control the disease. The comparative effects of graded doses of diaminazine aceturate (DA) and fixed doses of iron dextran and vitamin B complex were experimentally investigated in the treatment of Trypanosoma brucei brucei-infected albino mice. A total of 40 albino mice were used and were randomly divided into eight groups of five mice each. All the mice in all the groups except group H were infected with T. brucei brucei, but group H served as the negative control. Groups A and B were treated with graded doses of DA at 3.5 and 7 mg/kg body weight (bw), respectively, groups C, D, E and F were treated as follows: 3.5 mg/kg bw DA and 1 ml/10 kg bw iron dextran, 7.0 mg/kg bw DA plus 1 ml/10 kg bw iron dextran, 3.5 mg/kg bw DA, 1 ml/10 kg bw iron dextran and 1 ml/10 kg bw vitamin B complex and 7.0 mg/kg bw DA, 1 ml/10 kg bw iron dextran and 1 ml/10 kg bw vitamin B complex, respectively. Group G served as the infected untreated control. Parameters used to assess the effect of the drugs include rectal temperature, body weight changes, packed cell volumes, haemoglobin concentration, daily parasitaemia, clinical signs and survivability. By day 5 PI, all the infected mice had become parasitaemic but following treatment on day 7 PI, the parasites cleared from the blood of the mice in group B and D within 42 hours, groups A, C, E and F before 96 h. There was a significant reduction (P?<?0.05) in the mean body weight, packed cell volume and haemoglobin concentration and an increase in rectal temperature following infection but these were reversed by the various treatments. Iron dextran and vitamin B complex were combined with DA, there were improvement in their values, suggesting that combining trypanosomosis therapy with iron dextran and vitamin B complex will help in restoring the physiology of the animal.     

X-ray analysis of the effect of the 5-HT3 receptor antagonist granisetron on gastrointestinal motility in rats repeatedly treated with the antitumoral drug cisplatin

Cancer chemotherapy is associated with the development of numerous adverse effects, including nausea, emesis and other alterations in gastrointestinal (GI) motility. The administration of 5-HT₃ receptor antagonists has provided a clinical advance in the treatment of chemotherapy-induced vomiting but these drugs lose efficacy throughout chronic treatment. The effects of these drugs in experimental animals under chronic administration are not well known. Our aim was to study, using radiographic methods, the effect of the 5-HT₃ receptor antagonist granisetron on GI dysmotility induced in the rat by repeated cisplatin administration. First, invasive methods were used to select a dose of granisetron capable of reducing increased stomach weight due to acute cisplatin administration (6 mg/kg, ip). Second, rats received two intraperitoneal (ip) injections once a week for 4 weeks: granisetron (1 mg/kg, ip) or saline and, thirty min later, saline or cisplatin (2 mg/kg, ip). Body weight gain was measured throughout treatment. Radiological techniques were used to determine the acute (after first dose) and chronic (after last dose) effects of cisplatin and/or granisetron on GI motility. Repeated cisplatin-induced weight loss which granisetron did not prevent. Gastric emptying was delayed after the first cisplatin administration. Granisetron completely prevented this effect. After weekly administration, cisplatin-induced gastric dysmotility was enhanced and granisetron was not capable of completely preventing this effect. Granisetron prevents gastric emptying alterations, but its efficacy decreases throughout antineoplastic treatment. This might be due to the enhanced effect of cisplatin.     

Acute effects of vitamin B6 and fixed combinations of vitamin B1, B6, B12 on nociceptive activity evoked in the rat thalamus: Dose-response relationship and combinations with morphine and paracetamol

Summary Nociceptive activity was elicited in neurones of the thalamus by supramaximal electrical stimulation of afferent C fibres in the sural nerve of rats under urethane anesthesia. The fixed combination of vitamin B₁, B₆, B₁₂ (Neurobion^®) as well as of vitamin B₆ administered by i.p. injection dose-dependently reduced the evoked nociceptive activity. The ED₅₀ of Neurobion^® is 4.6 ml/kg (at 100 min after injection) and that of vitamin B₆ is 189mg/kg (at 90 min after injection). The minimum effective doses of Neurobion^® and vitamin B₆ are 0.5 ml/kg and 40 mg/kg, respectively. When Neurobion^® or vitamin B₆ were given at their minimum effective doses, and the minimum effective doses of morphine (0.025 mg/kg) or paracetamol (5 mg/kg) were injected i.v. 80 min later, i.e., when the maximum effect of higher doses of Neurobion^® or vitamin B₆was about to develop, no supraadditive effect developed. It is concluded that the antinociceptive effect caused by a single injection of Neurobion^® is largely due to vitamin B₆. Vitamin B₁₂ may contribute to this effect, whereas vitamin B₁ alone exhibited only a slight effect on nociception. Moreover, it appears that Neurobion^® produces its antinociceptive effect after a single injection and after repeated administration during several days by different mechanisms so that the effect of analgesic agents is not enhanced following a single injection of Neurobion^® but may be enhanced after repeated administration of the compound.     

Dexmedetomidine protects against cisplatin-induced acute kidney injury in mice through regulating apoptosis and inflammation

Objective and design

Cisplatin-based chemotherapy has been widely used in the perioperative period of cancer surgery, which exacerbates the risk of renal injury. In this study, we examined whether dexmedetomidine (DEX), a commonly used anesthetic adjuvant, shows a protective effect against cisplatin-induced acute kidney injury.

Materials

Acute kidney injury in mice was induced by cisplatin.

Treatments

Mice were administered with DEX 25 μg/kg or atipamezole 250 μg/kg (once a day, for 3 days) after cisplatin treatment.

Methods

The renal function and tubular damage score were evaluated at 72 h following cisplatin administration. Apoptotic tubular cells were detected by TUNEL assay. Caspase-3, p53, Bax, F4/80⁺ macrophages, CD3⁺ T cells, and NF-κB were examined by immunohistochemistry staining or Western blot. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein (MCP)-1 in kidney were measured using real-time polymerase chain reaction.

Results

DEX treatment preserved renal function and reduced tubular damage score of mice after cisplatin administration. Mice treated with DEX exhibited less apoptotic tubular cells in response to cisplatin insult, which was associated with decreased Bax and reduced activation of p53 and caspase-3. DEX suppressed the infiltration of macrophages and T cells into the kidneys following cisplatin treatment, which was involved in the inhibition of NF-κB activation and decreased expression of TNF-α, IL-1β, IL-6, and MCP-1. Furthermore, we showed that the renoprotective effect conferred by DEX may be related to α₂ adrenoceptor-dependent pathway.

Conclusion

We demonstrate that DEX protects the kidney against cisplatin-induced AKI by the regulation of apoptosis and inflammatory response.

     

Cisplatin nephrotoxicity: experimental and clinical studies

Cisplatin is currently one of the most used agents in the treatment of cancer and it is essential in the treatment of germ cell cancer. The use of the drug is hampered by side effects - especially renal toxicity which is dose limiting. The present work was undertaken to elucidate the pathophysiological mechanisms involved in cisplatin induced nephrotoxicity. Immediately after administration of cisplatin to dogs, renal blood flow (RBF) and glomerular filtration rate (GFR) remained unchanged, while proximal reabsorption rates decreased significantly. The cisplatin induced nephrotoxicity is thus initiated by an acute, mainly proximal tubular impairment, preceding alterations in renal hemodynamics. These data were confirmed in a micropuncture study in rats. At 48 to 72 hours after administration of cisplatin depressed renal function could be attributed to impairment of proximal as well as distal tubular reabsorptive capacities, now associated with increased renal vascular resistance. After administration of 4 cycles of 20 mg cisplatin/m2 d. for 5 days in humans, a small but significant decrease in 51Cr-EDTA clearance was observed. In the high-dose cisplatin group (40 mg/m2 d. for 5 days) a severe progressive decrease in GFR was observed during treatment and GFR remained decreased for up to 2 years after termination of treatment. The observation of an acute increase in N-acetyl-beta-D-glucosaminidase and beta-2-microglobulin indicates a primary tubular effect of cisplatin also in humans. A marked reduction of proximal tubular reabsorptive capacities of sodium and water was also observed in this group, together with a decrease in distal tubular function. These changes persist for at least 6 months after treatment. In the high-dose group proteinuria developed. This was mainly of tubular origin during cisplatin infusion and of glomerular origin between treatment cycles. Cisplatin remains one of the most potent antineoplastic agents ever developed. Further work should be performed to reduce its potential for renal toxicity.     

Vitamin E protects against monosodium glutamate-induced acute liver injury and hepatocyte ultrastructural alterations in rats

ABSTRACT

Food additives such as nitrates and nitrites, and monosodium glutamate (MSG) used in the food industry increase the risk of certain cancers and inflict damage to vital organs. We sought to determine whether the antioxidant vitamin E can protect against liver injuries induced by a toxic dose of MSG in a rat model of MSG-induced acute liver injury. The model group of rats received a daily dose of MSG (4 gm/kg) for 7 days, whereas the protective groups were either received a 100 mg/kg vitamin E plus MSG or 300 mg/kg vitamin E plus MSG for 7 days. Rats were then sacrificed at day 8. Transmission and light microscopy images revealed substantial liver tissue damage induced by MSG in the model group as demonstrated by apoptotic hepatocytes with Pyknotic nuclei and irregular nuclear membrane, and cytoplasm displayed many vacuoles, swollen mitochondria, dilated endoplasmic reticulum, dilated blood sinusoids and bundles of collagen fibers in extracellular space. Treatment of the model group with vitamin E showed a substantial protection of liver tissue and hepatocellular architecture by 300 mg/kg vitamin E compared to a partial protection by 100 mg/kg vitamin E. In addition, MSG significantly (p < .05) modulated serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), superoxide dismutase (SOD), and glutathione peroxidase (GPx), which were significantly (p < .05) protected with vitamin E. Thus, vitamin E at 300 mg/kg effectively protects against MSG-induced acute liver injury in rats, possibly via the inhibition of inflammation, and up-regulation of endogenous antioxidants.     

Increased dietary sodium induces COX2 expression by activating NFκB in renal medullary interstitial cells

High salt diet induces renal medullary cyclooxygenase 2 (COX2) expression. Selective blockade of renal medullary COX2 activity in rats causes salt-sensitive hypertension, suggesting a role for renal medullary COX2 in maintaining systemic sodium balance. The present study characterized the cellular location of COX2 induction in the kidney of mice following high salt diet and examined the role of NFκB in mediating this COX2 induction in response to increased dietary salt. High salt diet (8 % NaCl) for 3 days markedly increased renal medullary COX2 expression in C57Bl/6 J mice. Co-immunofluorescence using a COX2 antibody and antibodies against aquaporin-2, ClC-K, aquaporin-1, and CD31 showed that high salt diet-induced COX2 was selectively expressed in renal medullary interstitial cells. By using NFκB reporter transgenic mice, we observed a sevenfold increase of luciferase activity in the renal medulla of the NFκB-luciferase reporter mice following high salt diet, and a robust induction of enhanced green fluorescent protein (EGFP) expression mainly in renal medullary interstitial cells of the NFκB-EGFP reporter mice following high salt diet. Treating high salt diet-fed C57Bl/6 J mice with selective IκB kinase inhibitor IMD-0354 (8 mg/kg bw) substantially suppressed COX2 induction in renal medulla, and also significantly reduced urinary prostaglandin E₂ (PGE₂). These data therefore suggest that renal medullary interstitial cell NFκB plays an important role in mediating renal medullary COX2 expression and promoting renal PGE₂ synthesis in response to increased dietary sodium.     

Influence of repeated vitamin B administration on the frequency pattern analysed from rat brain electrical activity (tele-stereo-EEG)

Summary Recording of field potentials from different brain areas of freely behaving rats and subsequent spectral analysis of the signals has proved to be a most sensitive method in pharmacology. This new model is used to measure the effect on the electrical activity of the brain of repeated daily injections of 1 ml/kg of a vitamin B mixture (Neurobion^®, 1 ml containing 33.3 mg B₁, 33.3 mg B₆, and 0.333 mg B₁₂). Subacute application of the vitamin B combination for 1 week in a group of six rats resulted in changes in the power spectra, which became more prominent from day to day. Particularly increases in the power of the alpha₁ and beta range from the thalamus dominated the vitamin-induced changes. From the comparison with earlier results obtained with centrally acting serotonergic drugs, it is concluded that the pharmacodynamic action of the vitamin B mixture predominantly influences this transmitter system. The same group of animals, once challenged with a single dose of 0.2 mg/kg morphine before the repeated vitamin treatment, responded to the same challenge after the treatment in a more sensitive manner. Particularly power changes in the beta range were more pronounced. This higher sensitivity to a morphine challenge persisted for more than 1 week after the end of the vitamin treatment which points to a plastic change in serotonergic neurotransmitter control processes. The results obtained here may be linked to the antinociceptive properties of the vitamin B mixture and practical consequences may include a reduction of morphine dose for analgesia during repeated vitamin B treatment.     

The effect of <Emphasis Type="Italic">Iresine herbstii</Emphasis> Hook on some haematological parameters of experimentally induced anaemic rats

Iresine herbstii is fed to livestock in South-eastern Nigeria in the belief that it boosts their blood supply. The aim of this work is to study the effect of the methanolic extract of I. herbstii Hook on some blood parameters of experimentally induced anaemic albino rats. For acute toxicity study, graded doses of the methanolic leaf extract of I. herbstii at 10, 100, 1000, 1600, 2900 and 5000 mg/kg were administered orally to rats randomly allotted to six groups of three animals each and signs of toxicity were observed for 24 h. To evaluate its haematological effects, 100, 200, and 400 mg/kg of extract was administered orally to three out of five groups of six rats each for 14 days after the induction of acute blood loss anaemia. Parameters monitored were packed cell volume (PCV), haemoglobin concentration (Hb), weight gain and red blood cell counts (RBC). Phytochemical, proximate and nutritional analysis of the plant was done. I. herbstii had an LD₅₀?>?5000 mg/kg. Mean group weight gain and RBC were significantly (p?<?0.05) higher in treated than untreated groups. PCV and Hb did not differ significantly between the treated and untreated groups. Plant contained flavonoids; phenols; alkaloids; 22.85 % crude protein; 18.58 % ash; 9.62 % crude fibre; 1.5 % ether extract; 12.05 % moisture; vitamins A, C, E, B1, B3, B5, B6 and B12; zinc; iron; phosphorus; calcium; and magnesium. Methanolic extract of I. herbstii significantly improved red blood cell count of anaemic rats at the dose of 400 mg/kg bw and the body weights of anaemic rats at all treatment doses (100, 200 and 400 mg/kg bw).     

The effect of glutathione,vitamins B12 and B1. and rutin on the level of cholesterol in the brain,liver and blood in alimentary hypercholesterinemia

Summary The paper deals with materials on the effect of glutathione, vitamins B₁₂ and B₁, rutin and a combination of glutathione with vitamin B₁ or rutin on the cholesterol level in the blood, liver and brain during alimentary hypercholesterinemia. Experiments were staged on 266 chicks.Hypercholesterinemia was provoked by cholesterol-containing diet given for a period of 18 days. After the cessation of cholesterol administration, the chicks were given vitamin B₁₂ in a dose of 0.1 and 2, 0.2 mg of vitamin B₁ subcutaneously, rutin with food –100 mg per kg of body weight, glutathione –12.5 mg per 100 g of weight and combinations of glutathione with rutin or with vitamin B₁ in the aforesaid doses for a period of 10, 15, and 20 days. The chicks were decapitated after suspension of this treatment. Cholesterol concentration was determined in the blood, liver and brain. As established, cholesterol feeding markedly increased its content in the blood and liver. After discontinuance of cholesterol administration its content in the blood and liver drops almost to the initial level in 20 days. The hypocholesterizing effect of vitamin B₁₂ given in a dose of 0.1, of glutathione-rutin combination and of rutin alone was established. These were no changes in the cholesterol content of the brain tissue.(Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten Ékjsperimental'noi Biologii i Meditsiny, Vol. 51, No. 2, pp. 46–48, February, 1961     

Effect of quercetin against dichlorvos induced nephrotoxicity in rats

This study was carried out to determine the effect of quercetin against renal injury induced by dichlorvos (DDVP) in rats. Rats were randomly assigned to control, DDVP-treated (7.2 mg/kg bw), three different doses of quercetin-treated (2 mg/kg bw, 10 mg/kg bw, 50 mg/kg bw) and different doses of quercetin plus DDVP-treated groups. DDVP was administered daily to rats through their drinking water, and quercetin was administered by intragastric gavage for 90 days. By the end of the 90th day in the DDVP-treated group, the following indices significantly increased compared with the control (P < 0.01): activities of catalase, glutathione peroxidase and superoxide dismutase; level of malondialdehyde in kidney tissues; serum levels of creatinine and urea nitrogen; and level of β2-microglobulin, level of retinol-conjugated protein, and activity of N-acetyl-β-d-glucosaminidase in urine; by contrast, urine uric acid levels significantly decreased. However, in the quercetin (50 mg/kg bw) plus DDVP group, the aforementioned indices were significantly decreased compared with the DDVP-treated group (P < 0.05), except the urine uric acid levels were significantly increased (P < 0.05). Thus, rat exposure to DDVP caused renal injury, including renal tubular, glomerular filtration, and oxidative stress. These toxic effects were also regulated by high-dose quercetin. Histopathological examination revealed that exposure to DDVP induced extensive cell vacuolar denaturation, but milder histopathological alterations in the kidney tissues of rats co-treated with DDVP and quercetin (50 mg/kg bw) were observed. These results indicated that quercetin at 50 mg/kg bw can partly prevent the kidney injury induced by DDVP.     

Influence of Arecoline on Immune System: I. Short Term Effects on General Parameters and on the Adrenal and Lymphoid Organs

Abstract

Arecoline, a suspected carcinogenic/cocarcinogenic alkaloid was screened to explore in detail its immunomodulatory influence in murine model system. The oral LD₅₀ value for male mice was 371 mg/kg bw whereas it was 309 mg/kg bw for female mice. The subcutaneous LD₅₀ value for both sexes was 97 mg/kg bw. Only a marginal difference was observed in intraperitoneal LD₅₀ values between male (120 mg/kg bw) and female (109 mg/kg bw) mice. Arecoline was administered subcutaneously to male mice at subtoxic dose levels (5, 10, and 20 mg/kg bw) for 1, 2 and 3 weeks on a daily basis. In groups where significant decreases in body weight were present (at 20 mg/kg bw for both sexes), reductions in thymus weight were also noted. Spleen, mesenteric lymph nodes (MLN), liver, and kidney showed moderate reductions in their weights. Histopathological effects at 20 mg/kg bw included lymphocyte depletion of the thymic cortex, and the B and T lymphocyte areas in spleen and MLN. In concordance with the zona fasciculate hypertrophy of adrenals, corticosterone concentration in serum increased depending on the dose with a significant elevation at 20 mg/kg bw. While total protein, albumin, glucose, acid phosphatase and hemoglobin concentrations were not altered, increases in SG0T and SGPT levels were observed at the high dose. The white and red blood cell counts decreased in a dose-dependent manner. Marked reduction in cell number of thymus, and moderate effect on cellularity of spleen and MLN, were observed at 20 mg/kg bw. In vitro exposure of rat thymocytes to arecoline resulted in a biphasic oxygen consumption response with progressive increase in oxygen consumption, reaching a maximum value at 10^?5 M and decreasing sharply at 10^?3 M, Exogenously added substrates such as glucose, pyruvic acid and lactic acid retarded the fall in the oxygen consumption induced at 10^?3 M arecoline. These observations demonstrate the effects of arecoline on lymphoid organs, which may be due to its direct action or through the elevation of corticosterone.     

Tobramycin-induced changes in renal histology of fetal and newborn Sprague-Dawley rats.

Effects on renal development were studied using tobramycin (TBM) as a model compound. Pregnant Sprague-Dawley rats were injected i.p. with TBM at 30 or 60 mg/kg body weight/day on gestational days (GD) 10-19. Kidneys from dams and conceptuses were examined on GD 20 and on postnatal day (PD) 9. The dosing regimen caused in dams moderate proximal tubular alterations and increased concentrations in serum creatinine. Fetal kidneys showed granularity and swelling of proximal tubule cells at the 30 mg/kg dose, poor glomerular differentiation at the 60 mg/kg dose, increased glomerular density at both doses, and no changes on macroscopic examination at either dose. In newborns were observed a moderate developmental delay and tubular lesions at the higher dose, and dose-related increases of glomerular density and relative medullary area at both doses. All findings were more pronounced in males. A maturational disruption of the tubular structures possibly leading to increased glomerular density was attributed to TBM exposure during renal organogenesis in the rat.     

Immunohistochemical distribution of vitamin B12 R-binder in renal cell carcinoma

Summary Renal cell carcinomas and normal kidney tissues were examined for the expression of vitamin B₁₂ R-binder by the indirect immunoperoxidase method. In normal kidney tissue, the presence of the vitamin B₁₂ R-binder was shown to be confined to the straight portion (pars recta) of proximal tubules. Seven of the 38 cases of renal cell carcinoma (18%) expressed the vitamin B₁₂ R-binder antigen. This provides a further evidence of the proximal tubular nature of renal cell carcinoma, and suggests that a small proportion of renal cell carcinomas originate from the straight portion of the renal proximal tubules.