Study of Na+ and Water Transport in the Pigeon and Chicken Kidney by Lithium Clearance Method under Conditions of Water and Salt Load: Regimes of Renal Net Reabsorption and Net Secretion of Li+

The water (intestinally) and salt (intravenously) loads of a sufficient intensity (about 120 ml water or 9 mmol NaCl per kg body mass) caused a reversible conversion (of duration of 30–40 min) in the renal Li transport, i.e., transition from net reabsorption of this ion (FE_Li = C_Li/GFR < 1) to its net secretion (FE_Li > 1), where C_Li—lithium clearance, GFR—glomerular filtration rate, ⁶⁵ZnDTPA clearance. Maximal values of the fractional lithium excretion (FE_Li) amounted to about 1.5 and 2.0 after the water and salt loads, respectively. A repeated salt load (4–5 NaCl injections by 9 mmol/kg at 20–40 min intervals) induced a long (2–3 h) net secretion of lithium in the chicken kidney. This regime of renal functioning was characterized by abundant urination (20–30 ml/kg/h) and a substantial increase of the Na⁺ concentration in blood plasma (from 138 ± 9 to 172 ± 10 mM, the mean ( standard deviation) and in urine (to 157 ± 19 mM). The data obtained were considered in terms of a hypothesis suggesting that the renal lithium secretion indicates the appearance of net water and Na⁺ secretion in the proximal tubule of the avian kidney in response to water and salt load. The fractional reabsorption of Na⁺ and water in the chicken kidney were calculated by means of lithium clearance during both the net reabsorption and the secretion of lithium in the kidney. In the former regime of renal functioning (FE_Li < 1), regardless of changes in lithium reabsorption (up to its complete cessation at FE_Li = 1), the kidney as a whole reabsorbs about 99% of filtered Na⁺, while distal reabsorption of this ion accounts for about 98%. The corresponding values for water reabsorption are about 96 and 92%, respectively. At FE_Li > 1, the fractional reabsorption of Na⁺ and water decrease significantly: the minimal values amount to about 60%, while the mean values, about 80%.     

Regulation of canine renal vesicle Pi transport by growth hormone and parathyroid hormone

Renal phosphate (P_i) reabsorption is increased by growth hormone (GH) and decreased by parathyroid hormone (PTH). Na⁺-stimulated P_i transport across the brush border membrane of the proximal tubule is the initial step in the process of P_i reabsorption. To determine whether changes in P_i reabsorption induced by GH or PTH are accompanied by changes in brush border membrane Na⁺-gradient-stimulated P_i transport, we examined the effect of in vivo GH and PTH administration and thyroparathyroidectomy on P_i transport by isolated brush border membrane vesicles prepared from canine kidney. In experiments in which the effect of PTH administration was examined, the same animal provided the control kidney (before PTH administration) and the experimental kidney (after PTH administration). The Na⁺-gradient P_i overshoot in vesicles isolated from normal, GH-treated and thyroparathyroidectomized dogs was increased after in vivo PTH administration. GH administration and thyroparathyroidectomy increased the height of the overshoot compared to normal. PTH administration decreased the apparent $\text{V}$ value by 44% in vesicles from normal animals. The apparent $\text{V}$ value was increased, compared to normal, by GH (34%) and thyroparathyroidectomy (57%). PTH administration decreased the apparent $\text{V}$ in both the latter groups. GH administration to thyroparathyroidectomized dogs further increased the apparent $\text{V}$. Changes in the apparent $\text{V}$ paralleled changes in P_i reabsorption in vivo induced by experimental manipulations. We conclude that changes in renal P_i reabsorption induced by GH were like those induced by PTH, accompanied by changes in the Na⁺-stimulated P_i transport system in the renal brush border membrane, and that the effect of PTH on vesicular P_i transport in GH-treated dogs did not differ from the effect on vesicles from normal animals.     

Vasopressin and prostaglandin <Emphasis Type="Italic">E</Emphasis><Subscript>2</Subscript> as regulators of renal function during children’s development

The main physicochemical parameters of blood serum (the osmolality and concentrations of Na⁺, K⁺, Ca²⁺, and Mg²⁺) determined in 314 children (from newborn infants to 17-year-old adolescents) and 25 adults were found to be virtually constant throughout the postnatal period, which was due to the high effectiveness of the systems responsible for their stabilization. From the first postnatal days until puberty, prostaglandin E₂ (PGE₂) and arginine vasopressin (AVP) are involved in the regulation of renal water excretion. In infants, during their first postnatal months, the excretion of solute-free water is correlated with the excretion of PGE₂. Adult-type effects of AVP on the reabsorption of solute-free water were observed in children only after 12 postnatal months. A change in the reabsorption of ions in the thick ascending limb of Henle’s loop was shown to be involved in the regulation of the volume of urine excreted. AVP and PGE₂ are also involved in the regulation of the distal segment of the nephron and collecting tubules, but their influence on the volume and composition of urine is age-dependent.     

In Situ Characterization of Renal Insulin Receptrors in the Rat

Abstract

Insulin regulates carbohydrate metabolism, and water, sodium, potassium, and phosphate reabsorption in the kidney by binding to specific receptors. Insulin receptors have been identified in the kidney using membrane preparations obtained from both glomeruli and tubules. In this study, an autoradiographic technique was used to characterize insulin receptors in the rat kidney. Frozen tissue sections were preincubated to remove endogenously bound insulin, incubated in a buffer containing 200 pM 12sl-Tyr-insulin, washed, and dried before exposure on Ultrofilm. Binding density was assessed by computerized microdensitometry. In the cortex, binding density was comparable in glomeruli and tubules. In the medulla, bound radioligand was found primarily in longitudinal structures traversing the outer portion, presumably corresponding to vascular bundles, and in the inner portion. Scatchard analysis of competition binding data resulted in curvilinear profiles, indicating either two classes of receptors with different affinity or the presence of a single class of receptors with a negative cooperative hormone-receptor interaction. Data analyzed for a two-site model showed one receptor site with Kd of 0.39f0.14 nmol/l and Bmax of 3. M. O × 1010 receptordmma and another site with Kd of 0.30fl.1 pmoVl and a Bmax of 3.2 × 1013 receptordmms. Thus, in situ autoradiography can be used to determine distribution and binding characteristics of insulin receptors in rat kidney and might be employed in receptor studies on rat models of human disease.     

Effect of oleamide on water and sodium ion transport in osmoregulatory organs of vertebrates

In the frog Rana temporaria L., oleamide solution (10 μmole/L) applied to the isolated basal surface of the skin augmented the short-circuit current (SCC) from 59.8 ± 2.5 to 78.2 ± 1.4 μA/cm². When applied to the serous membrane of the urinary bladder, oleamide (1 μmole/L) induced more than a 30-fold increase in osmotic water permeability. The addition of argininevasotocin against the background of oleamide further increased SCC across the skin and osmotic water permeability in the bladder. In Wistar rats, intraperitoneal injection of oleamide (0.1 μmole/L per 100 g of body weight) to non-anesthetized animals after water load reduced diuresis by 22% and increased solute-free water reabsorption and urinary sodium excretion by 31% and 55%, respectively, but did not affect urinary potassium excretion. These findings provide evidence of the similarity between the effects of oleamide and nonapeptide neurohypophyseal hormones on water and ion transport in epithelial cells of osmoregulatory organs in vertebrates.     

Effects of exenatide on glycemia and renal water and ion excretion differ in frogs and rats

The aim of this study was to compare the effects of exenatide, a glucagon-like peptide-1 (GLP-1) mimetic, on glucose and water–salt homeostasis in animals with different levels of renal proximal tubular reabsorption, rats (Rattus norvegicus) and frogs (Rana temporaria). Following the glucose tolerance test, in rats exenatide promoted fast recovery of normoglycemia, whereas in frogs it delayed this process. In water-loaded rats, exenatide augmented solute-free water clearance and enhanced natriuresis in furosemide-treated animals. In frogs, exenatide did not alter the urinary flow rate, urinary sodium excretion and solute-free water clearance under water diuresis and furosemide treatment. It is suggested that the involvement of GLP-1 in regulation of water–salt homeostasis in mammals was preceded by a key evolutionary transformation, the increase in the glomerular filtration rate and proximal tubular reabsorption.     

Effect of circulatory congestion on the components of pulmonary diffusing capacity in morbid obesity

Objective: Obese patients without clinically apparent heart disease may have a high output state and elevated total and central blood volumes. Central circulatory congestion should result in elevated pulmonary diffusing capacity (D_LCO) and capillary blood volume (V_c) reflecting pulmonary capillary recruitment; however, the effect on membrane diffusion (D_m) is uncertain. We examined D_LCO and its partition into V_c and D_m in 13 severely obese subjects (BMI = 51 ± 14 kg/m²) without manifest cardiopulmonary disease before and after surgically induced weight loss. Research Methods and Procedures: D_LCO and its partition into V_c and D_m [referenced to alveolar volume (V_A)] as described by Roughton and Forster, total body water by tritiated water, and fat distribution by waist‐to‐hip ratio were performed. Results: Despite normal D_LCO (mean 98 ± 16% predicted), V_c/V_A was increased (mean 118 ± 30% predicted), and D_m/V_A was reduced (mean 77 ± 34% predicted). Nine of 13 subjects were restudied after weight loss (mean 52 ± 43 kg); V_c/V_A decreased to 89 ± 18% predicted (p = 0.01), and D_m/V_A increased to 139 ± 30% predicted (p < 0.01). Increasing total body water was associated with both increasing V_c (r = 0.74, p = 0.01) and increasing waist‐to‐hip ratio (r = 0.65, p = 0.02), indicating that circulatory congestion increases with increasing central obesity. Discussion: Severely obese subjects without manifest cardiopulmonary disease may have increased V_c indicating central circulatory congestion and reduced D_m suggesting associated alveolar capillary leak, despite normal D_LCO. Reversibility with weight loss is in accord with reversibility of the hemodynamic abnormalities of obesity.     

GABAA receptors in nucleus accumbens shell mediate the hyperphagia and weight gain following haloperidol treatment in rats

AimsWeight gain is a common outcome of antipsychotics therapy in schizophrenic patients. However, the underlying neuronal mechanisms are unclear. The present study was undertaken to investigate the role of GABA_A receptors within the framework of nucleus accumbens shell (AcbSh) in haloperidol-induced hyperphagia and body weight gain in sated rats.Main methodsIn acute studies, GABA_A receptor agonists muscimol, diazepam or antagonist bicuculline were administered by AcbSh route, alone or in combination with haloperidol (intraperitoneal/ip). Immediately after these treatments, preweighed food was offered to the animals at commencement of dark phase. Cumulative food intake was measured at 2 and 6 h post-injection time-points. Furthermore, effects of subacute haloperidol treatment, alone or in combination with muscimol, diazepam or bicuculline, on food intake and body weight were investigated.Key findingsWhile acute treatment with haloperidol, muscimol or diazepam dose dependently stimulated the food intake, bicuculline suppressed the same. Prior administration of muscimol (20 ng/rat, intra-AcbSh) and diazepam (5 µg/rat, intra-AcbSh) significantly potentiated, whereas bicuculline (40 ng/rat, intra-AcbSh) negated the hyperphagic effect of acute haloperidol (0.005 or 0.01 mg/kg/rat, ip). Subacute administration of haloperidol (0.01 mg/kg/rat/day, ip) for 15 days produced increase in food intake and body weight. Although, concomitant administration of muscimol (20 ng/rat/day, intra-AcbSh) or diazepam (5 μg/rat/day, intra-AcbSh) markedly enhanced, bicuculline (40 ng/rat/day, intra-AcbSh) prevented the subacute haloperidol-induced hyperphagia and weight gain.SignificanceThe results of present study suggest that increased food intake and body weight following haloperidol treatment in rats, may be mediated via AcbSh GABA_A receptors.     

Lack of Interaction of Vasopressin with its Antisense Peptides: A Functional and Immunological Study

Abstract

The peptide encoded in the 5″ to 3″ direction by rat vasopressin complementary RNA, rat PVA (H-Ser-Ser-Trp-Ala-Val-Leu-Glu-Val-Ala-OH) and the corresponding bovine PVA (H-Ala-Pro-Trp-Ala-Val-Leu-Glu-Val-Ala-OH) were investigated with respect to their interaction with [8-arginine] vasopressin (AVP) and V₂ vasopressin receptor binding and function. Rat or bovine PVA did neither affect the binding of the hormone to the V₂ receptor of bovine kidney membranes and LLC-PK₁ pig kidney cells nor influence the AVP-induced cAMP-production in LLC-PK₁ cells. Rat PVA was further investigated by the use of vasopressin-specific polyclonal and monoclonal antibodies with differnt affinity and epitope specifity. Consistent with receptor binding studies no inhibition of [³H]AVP-binding in fluid- or solid-phase antibody binding tests after preincu-bation with PVA was found. Direct interaction of rat PVA and [³H]AVP measured on solid surface was not observed in contrast to specific binding of the hormone with NP II and antibodies. In our study no evidence for an interaction of AVP and its antisense peptides was found.     

Renal responses to atrial natriuretic factor in hydrated and hydropenic dogs

Atrial natriuretic factor (ANF 101-126) was compared to the standard diuretics, furosemide and hydrochlorothiazide, and to the vasodilator, acetylcholine in hydrated and dehydrated anesthetized dogs. ANF 101-126 (20 pmole/kg/min, ira) modestly reduced solute-free water clearance in water-loaded dogs and slightly lowered free water reabsorption in dehydrated animals. This pattern of responses most closely resembled those produce by 10 mg/kg, ira of the distally-acting diuretic, hydrochlorothiazide and a natriuretic dose of acetylcholine (2.5 micrograms/kg/min, ira). In contrast, the loop diuretic, furosemide (1 mg/kg, ira) drastically suppressed both free water clearance and reabsorption. ANF 101-126 produced changes in free water handling which were not readily distinguishable from those induced by either hydrochlorothiazide, a distally-acting diuretic, or acetylcholine, a vasodilator.     

Renal compensation for cecal loss in Gambel's quail (Callipepla gambelii)

Some studies have implicated the avian digestive cecae as important sites of water and solute reclamation working in concert with the lower intestine and the kidneys as part of an integrated osmoregulatory system. In Gambel's quail (Callipepla gambelii), we studied compensatory adjustments in renal function on days 6–7 and 16–17 following ligation of cecae. Plasma osmolality (P_osm) varied significantly between groups with sham-operatd birds (Cs), with an average (P_osm) of 348 mOsm/kg H₂O and quail with ligated cecae (Cx) having a (P_osm) of 355 mOsm/kg H₂O. We detected no change in the rate of glomerular filtration (GFR) between experimental and control groups either shortly after cecectomy or after 16–17 d following surgery. Regression analysis of GFR and urine flow rate (V) showed that Cx birds had a significantly lower V at a given GFR than did controls, evidence that Cx quail absorbed more fluid in their renal tubules. Increased fluid reabsorption was apparently driven by an enhanced reabsorption of sodium. Indeed, sodium excretion was lower in Cx quail as compared to sham-operated birds. On days 6–7, Cx quail drank more water than Cs birds, but by days 16–17 drinking rates were similar. At the end of the experiments, Cx quail showed a proliferation of microvilli along the apical membrane of the rectum, an adjustment consistent with the idea that the rectum alters its absorption capacity to adjust for the loss of cecal function.     

Energetics of sodium transport in the kidney: Saturation transfer 31P-NMR

³¹P-NMR has been used to quantify inorganic phosphate (P_i) and high-energy phosphates in the isolated, functioning perfused rat kidney, while monitoring oxygen consumption, glomerular filtration rate and sodium reabsorption. Compared with enzymatic analysis, 100% of ATP, but only 25% of ADP and 27% of P_i are visible to NMR. This is indicative that a large proportion of both ADP and P_i are bound in the intact kidney. NMR is measuring free, and therefore probably cytosolic concentrations of these metabolites. ATP synthesis rate, measured by saturation transfer NMR shows the P:O ratio of 2.45 for the intact kidney. This is close to the theoretical value, suggesting the NMR visible pool is that which is involved in oxidative phosphorylation. The energy cost of Na transport, calculated from the theoretical Na:ATP of 3.0 exceeded the measured rate of ATP synthesis. Instead, Na:ATP for active transport in the perfused kidney was 12. Since the phosphorylation potential ($\text{[}\text{ATP}\text{]}\text{[}\text{ADP}\text{]×[}\text{P}{}_{\mathrm{i}}\text{]}$) by NMR was 10 000 M^?1, the free-energy of ATP hydrolysis was 52 kJ/mol. Using this figure, the rate of ATP hydrolysis observed could fully account for the observed rate of sodium reabsorption.     

Synthesis and study of effect of analogs of conopressin S on excretion of ions and water by rat kidney

There were studied effects of analogs of conopressin S—a peptide of the vasopressin family with amino acid replacement at the 2nd and 4th positions (characteristic of invertebrate peptides)—on transport of water and ions in the rat kidney. Administration to female Wistar rats of 1-deamino-conopessin S produced a weak action on water transport and had no effect on K⁺ and Na⁺ excretion. Its analog, 1-deamino-Tyr²-conopressin S, caused antidiuretic and kaliuretic action without affecting Na⁺ excretion. Evaluation of significance of the variant of optic arginine isomer at the 4th and 8th position of the molecule for the antidiuretic and kaliuretic action of the peptide showed that 1-deamino-Tyr²,D-Arg⁴-conopressin S and 1-deamino-Tyr²,D-Arg^{4, 8}-conopressin S did not affect the urinary K⁺ excretion and renal water reabsorption, whereas action of 1-deamino-Tyr²,D-Arg⁸-conopressin S did not differ from action of 1-deamino-Tyr²-conopressin S. Thus, it has been established that the selective kaliuretic action of conopressin S analogs on rat kidney depends on the presence of tyrosine at the 2nd and of L-arginine, but not of D-argynine, at the 4th position of the molecule.     

Role of V1- and V2-receptors in mechanism of physiological paradox--an increase of reabsorption of the solute free water and simultaneous rise of diuresis

In experiments on non-anesthetized rats with administration into stomach of water (5 ml/100 g body mass) direct correlation has been found between an increase of diuresis and excretion of solute free water (r = 0.98, p < 0.01), while after injection to these animals of 5 x 10(-11) M arginine-vasotocin - between an increase of diuresis and simultaneous rise reabsorption of solute free water (r = 0.8, p < 0.01). The rise of diuresis after the vasotocin injection is due to inhibition of sodium re- absorption, with the solute excretion fraction increasing from 2.6 +/- 0.2 % to 11.9 +/- 1.2, p < 0.001. A similar physiological paradox - an increase of diuresis with the simultaneous increase of reabsorption of solute free water - has been revealed at night hours in children with tendency for nocturnal enuresis (r = 0.64, p < 0.01). Mechanism responsible for this phenomenon consists in a rise of diuresis due to a decrease of sodium ion reabsorption in the ascending Henle loop limb. A problem is discussed of the homeostatic significance of a decrease of sodium reabsorption combined with an increase of solute-free water reabsorption; it is suggested that this phenomenon is based on a redistribution of reabsorption inside the nephron - a decrease of ion and water reabsorption in the initial parts of the nephron distal segment and an increase of solute free water reabsorption with the antidiuretic hormone-stimulated high osmotic permeability of terminal parts of renal tubules. An intraperitoneal injection of V1-anatagonist (OPC-21268) decreased the natriuretic component of response to arginine-vasotocin, while injection of V2-antagonist (OPC-31260) eliminated the antidiuretic component.     

Antimuscarinic potency and functional selectivity of oxotremorine analogs at muscarinic receptor subtypes in the rat.

The potency of six antimuscarinic oxotremorine analogs at sympathetic ganglionic M1 and brainstem M2 muscarinic receptors was compared in the rat. Inhibition of the pressor effects of McNA343 or physostigmine was used as functional indicators of M1 and M2 blockade, respectively. 50% inhibitory doses (ID50) were calculated against both cholinomimetics. Of the analogs, PCA-10 was the most potent, with ID50 values of 0.16 and 0.11 mumol/kg versus McNA343 and physostigmine, respectively. A correlation analysis indicated that these analogs did not functionally discriminate between responses mediated by neuronal M1 or M2 muscarinic receptors in vivo. In contrast, these analogs antagonized M1 ganglionic responses at doses which produced negligible antagonism at cardiac and vascular M2 receptors.     

Enhanced glucose tolerance in the Brattleboro rat

[Arg⁸]-vasopressin (AVP) plays a crucial role in regulating body fluid retention, which is mediated through the vasopressin V₂ receptor in the kidney. In addition, AVP is involved in the regulation of glucose homeostasis via vasopressin V_1A and vasopressin V_1B receptors. Our previous studies demonstrated that vasopressin V_1A receptor-deficient (V_1AR−/−) and V_1B receptor-deficient (V_1BR−/−) mice exhibited hyperglycemia and hypoglycemia with hypoinsulinemia, respectively. These findings indicate that vasopressin V_1A receptor deficiency results in decreased insulin sensitivity whereas vasopressin V_1B receptor deficiency results in increased insulin sensitivity. In addition, vasopressin V_1A and vasopressin V_1B receptor double-deficient (V_1ABR−/−) mice exhibited impaired glucose tolerance, suggesting that the effects of vasopressin V_1B receptor deficiency do not influence the development of hyperglycemia promoted by vasopressin V_1A receptor deficiency, and that the blockage of both receptors could lead to impaired glucose tolerance. However, the contributions of the entire AVP/vasopressin receptors system to the regulation of blood glucose have not yet been clarified. In this study, to further understand the role of AVP/vasopressin receptors signaling in blood glucose regulation, we assessed the glucose tolerance of AVP-deficient homozygous Brattleboro (di/di) rats using an oral glucose tolerance test (GTT). Plasma glucose and insulin levels were consistently lower in homozygous di/di rats than in heterozygous di/+ rats during the GTT, suggesting that the blockage of all AVP/vasopressin receptors resulting from the AVP deficiency could lead to enhanced glucose tolerance.     

Folate-dependent hydrolysis of acetyl-coenzyme A by recombinant human and rodent arylamine N-acetyltransferases

Arylamine N-acetyltransferases (NATs) are drug and xenobiotic metabolizing enzymes that catalyze the N-acetylation of arylamines and hydrazines and the O-acetylation of N-hydroxy-arylamines. Recently, studies report that human NAT1 and mouse Nat2 hydrolyze acetyl-coenzyme A (AcCoA) into acetate and coenzyme A in a folate-dependent fashion, a previously unknown function. In this study, our goal was to confirm these findings and determine the apparent Michaelis–Menten kinetic constants (V_max and K_m) of the folate-dependent AcCoA hydrolysis for human NAT1/NAT2, and the rodent analogs rat Nat1/Nat2, mouse Nat1/Nat2, and hamster Nat1/Nat2. We also compared apparent V_max values for AcCoA hydrolysis and N-acetylation of the substrate para-aminobenzoic acid (PABA). Human NAT1 and its rodent analogs rat Nat2, mouse Nat2 and hamster Nat2 catalyzed AcCoA hydrolysis in a folate-dependent manner. Rates of AcCoA hydrolysis were between 0.25–1% of the rates for N-acetylation of PABA catalyzed by human NAT1 and its rodent orthologs. In contrast to human NAT1, human NAT2 and its rodent analogs rat Nat1, mouse Nat1, and hamster Nat1 did not hydrolyze AcCoA in a folate-dependent manner. These results are consistent with the possibility that human NAT1 and its rodent analogs regulate endogenous AcCoA levels.     

Molecular basis for prostaglandin potency. III. Tests of the significance of the “hairpin conformation” in biorecognition phenomena

Prostaglandin analogs of the PGF_2α, 15-epi-PGF_2α, and PGE₂ type bearing the following methyl substitution patterns — 15-Me, 16, 16-(Me)₂, 17, 17-(Me)₂, and 18, 18, 20-(Me)₃ — and analogs constrained to “hairpin” alignment [via 1, (ω-1)-olide formation] and to “non-hairpin” arrangements [via 1,9- and 1,15-olide formation] are compared in the following biological assays: contraction of uterine and gastro-intestinal smooth muscle strips, luteolytic antifertility potency in the hamster, binding affinity to two different PGF₂α-receptor preparations from bovine corpora lutea, binding to the PGE-specific receptors from rat kidney and liver, inhibition of ADP-induced aggregation of human platelet-rich-plasma, and the effect on rat blood blood pressure. The methylated prostaglandins were also converted to the corresponding prostacyclins and examined as to action on the platelet and on rat blood pressure. All evidence points to topographically distinct receptors for F₂α-, E- and I₂-type prostaglandins. Cross-reactivity is reduced in most of the analogs examined. Independent of the target organ or tissue, the receptors show common features based on the functional class of PG recognized. “Hairpin” alignment improves binding (and potency) only for the PGF₂α specific assays. PGE-specific binding and potency is disrupted to an increasing extent as the chain branching point is moved $\text{further}$ from the 15-hydroxyl center. In contrast 16, 16-dimethylation is particularly disruptive for the PGI₂/E₁platelet receptor interaction.     

Ameliorative effect of carnosine and N-acetylcysteine against sodium nitrite induced nephrotoxicity in rats

The widespread use of sodium nitrite (NaNO₂) for various industrial purposes has increased human exposure to alarmingly high levels of nitrate/nitrite. Because NaNO ₂ is a strong oxidizing agent, induction of oxidative stress is one of the mechanisms by which it can exert toxicity in humans and animals. We have investigated the possible protection offered by carnosine (CAR) and N-acetylcysteine (NAC) against NaNO ₂-induced nephrotoxicity in rats. Animals orally received CAR at 100 mg/kg body weight/d for seven days or NAC at 100 mg/kg body weight/d for five days followed by a single oral dose of NaNO ₂ at 60 mg/kg body weight. The rats were killed after 24 hours, and the kidneys were removed and processed for various analyses. NaNO ₂ induced oxidative stress in kidneys, as shown by the decreased activities of antioxidant defense, brush border membrane, and metabolic enzymes. DNA-protein crosslinking and DNA fragmentation were also observed. CAR/NAC pretreatment significantly protected the kidney against these biochemical alterations. Histological studies supported these findings, showing kidney damage in NaNO ₂-treated animals and reduced tissue impairment in the combination groups. The protection offered by CAR and NAC against NaNO ₂-induced damage, and their nontoxic nature, makes them potential therapeutic agents against nitrite-induced nephrotoxicity.     

Regulation of expression of antioxidant enzymes by vitamin E and curcumin in <Emphasis Type="SmallCaps">l</Emphasis>-thyroxine-induced oxidative stress in rat renal cortex

The present study investigates the antioxidative effects of vitamin E and curcumin against l-thyroxine (T₄)-induced oxidative stress in renal cortex of adult male rats. Rats were made hyperthyroid by administration of l-thyroxine (0.0012%) in their drinking water for 30 days. Vitamin E (200 mg/kg body weight/day) and curcumin (30 mg/kg body weight/day) were supplemented singly or in combination orally for 30 days along with l-thyroxine treatment. The elevated level of oxidative stress parameters (lipid peroxidation and protein carbonylation) and decline level of small antioxidant molecules (reduced glutathione and ascorbic acid) in renal cortex of T₄-treated rats were restored back by supplementation of vitamin E or/and curcumin. Increased superoxide dismutase and catalase activities in kidney cortex of T₄-treated rats were ameliorated in response to vitamin E or/and curcumin treatment. The elevated translated product of Cu/Zn-SOD, Mn-SOD and catalase in T₄-treated rats were differentially reduced by the administration of vitamin E and curcumin independently or in combination. Cu/Zn-SOD expression was ameliorated by both vitamin E and curcumin independently or in combination, whereas Mn-SOD expression was ameliorated by the supplementation of vitamin E or curcumin independently. However, the expression of catalase was alleviated by only supplementation of vitamin E to T₄-treated rats. The results suggest that both vitamin E and curcumin may play an important role in protecting T₄-induced oxidative stress in rat renal cortex by differentially modulating the activities of antioxidant enzymes and oxidative stress parameters.