Aminoglycosides, including gentamicin, have been used as antibiotics for the various infections by gram-negative bacteria. However, there are some restrictions for using these drugs. Gentamicin, a typical aminoglycoside, has the side effect of nephrotoxicity, including polyuria, glycosuria, proteinuria, glomerulonephritis, and uremia. The aims of this study were to examine the prevention or reduction effects of Jinmootang on the gentamicin-induced nephrotoxicity and to investigate the possible mechanisms on the effect of Jinmootang. The subcutaneous injections of 60mg of gentamicin per kg of boby weight to Sprague-Dawley rats for 8 days induced typical symptoms of nephrotoxicity by aminoglycosides. 0.6ml of water extract Jinmootang (100ml/chup) was orally treated in the experimental animal. 24-hour urine was collected with the metabolic cage and plasma was sampled from the abdominal aorta. The plasma concentration of sodium was significantly decreased by the treatment of gentamicin but it was not-significantly changed by the treatment of Jinmootang to the animal. The concentration of potassium was greatly decreased in the gentamicin-treated animals. However. it was returned to the normal level in the Jinmootang-treated animals. The concentrations of creatinine and urea were increased by gentamicin treatment. But, Jinmootang reduced these concentrations. Nevertheless, the osmolalities of plasma in both group were not different from each other. Even though the plasma concentration of aldosterone was not significantly changed, the mean value was increased by the gentamicin intoxication. The concentration of aldosterone was decreased by the treatment of Jinmootang. The reduction of aldosterone level in plasma could be a factor to improve the hypokalemia. The fractional excretion of potassium was much higher than normal by the treatment of gentamicin and it was decreased by 50% in the Jinmootang-treated rats. Therefore, the reabsorption of potassium was significantly increased by the treatment of Jinmootang, even though the filtered load of potassium in the experimental group was much highter than control. Even though the concentration of plasma aldosterone was decreased by the treatment of Jinmootang, the fractional excretion of sodium was not increased, slightly lower. These data suggested that Na reabsorption was increased in the proximal tubule by Jinmootang. The filtered load of glucose in the Jinmootang-treated group was greater than in control. Nevertheless, the fractional excretion of glucose in the experimental group was not different from that in control. These results indicate that glucose reabsorption was increase in the proximal tubule by Jinmootang treatment. The results of this study suggest that Jinmootang could improve the some nephrotoxic symptoms induced by gentramicin treatment. Hypokalemia, the reduced glomerular filtration rate, and dysfunctions of renal proximal tubule and distal nephron were significantly recovered to normal level. The increase of glomerular filtration rate by Jinmootang might contribute to eliminate the waste product, including creatinine and urea, and/or gentamicin through the kidney.
Kim, Andrew HyoungJin;Yoon, Sumin;Lee, Yujin;Lee, Jieon;Bae, Eunjin;Lee, Hajeong;Kim, Dong Ki;Lee, SeungHwan;Yu, Kyung-sang;Jang, In-Jin;Cho, Joo-Youn
Journal of Korean Medical Science
/
v.33
no.53
/
pp.298.1-298.10
/
2018
Background: The renal function of individuals is one of the reasons for the variations in therapeutic response to various drugs. Patients with renal impairment are often exposed to drug toxicity, even with drugs that are usually eliminated by hepatic metabolism. Previous study has reported an increased plasma concentration of indoxyl sulfate and decreased plasma concentration of $4{\beta}$-hydroxy (OH)-cholesterol in stable kidney transplant recipients, implicating indoxyl sulfate as a cytochrome P450 (CYP) inhibiting factor. In this study, we aimed to evaluate the impact of renal impairment severity-dependent accumulation of indoxyl sulfate on hepatic CYP3A activity using metabolic markers. Methods: Sixty-six subjects were enrolled in this study; based on estimated glomerular filtration rate (eGFR), they were classified as having mild, moderate, or severe renal impairment. The plasma concentration of indoxyl sulfate was quantified using liquid chromatography-mass spectrometry (LC-MS). Urinary and plasma markers ($6{\beta}$-OH-cortisol/cortisol, $6{\beta}$-OH-cortisone/cortisone, $4{\beta}$-OH-cholesterol) for hepatic CYP3A activity were quantified using gas chromatography-mass spectrometry (GC-MS). The total plasma concentration of cholesterol was measured using the enzymatic colorimetric assay to calculate the $4{\beta}$-OH-cholesterol/cholesterol ratio. The correlation between variables was assessed using Pearson's correlation test. Results: There was a significant negative correlation between MDRD eGFR and indoxyl sulfate levels. The levels of urinary $6{\beta}$-OH-cortisol/cortisol and $6{\beta}$-OH-cortisone/cortisone as well as plasma $4{\beta}$-OH-cholesterol and $4{\beta}$-OH-cholesterol/cholesterol were not correlated with MDRD eGFR and the plasma concentration of indoxyl sulfate. Conclusion: Hepatic CYP3A activity may not be affected by renal impairment-induced accumulation of plasma indoxyl sulfate.
This study examined the association between hypertension (HTN), estimated glomerular filtration rate (eGFR), and urine microalbumin/creatinine ratio (ACR) in Korean adults. Data for 8,922 adults (3,941 men and 4,981 women) aged ≥20 years from the Sixth Korean National Health and Nutrition Examination Survey VI (2013~2014) were analyzed. In men, after adjusting for the related variables, the odds ratios (ORs) of HTN [systolic blood pressure (SBP) ≥140 mmHg, diastolic blood pressure (DBP) ≥90 mmHg, or use of HTN medications] were significantly higher in the decreased eGFR group [eGFR <60 mL/min/1.73 ㎡, 1.98 (95% CI, 1.21~3.24)], elevated ACR group [ACR ≥30 mg/g, 2.03 (95% CI, 1.54~2.69)], and decreased eGFR plus elevated ACR group [eGFR <60 mL/min/1.73 ㎡ and ACR ≥30 mg/g, 6.03 (95% CI, 2.82~12.92)] than in the normal group (eGFR ≥60 mL/min/1.73 ㎡ and ACR <30 mg/g). In women, after adjusting for the related variables, the ORs of HTN were significantly higher in the decreased eGFR group (2.29, 95% CI, 1.27~4.13), elevated ACR group (2.22, 95% CI, 1.68~2.94), and decreased eGFR plus elevated ACR group (10.77, 95% CI, 3.89~29.82) than the normal group. In conclusion, HTN was associated with a decreased eGFR and elevated ACR in Korean men and women. In addition, the prevalence of HTN increased greatly when a decreased eGFR and elevated ACR occurred simultaneously.
The regulations of renal function and renin release are influenced by neural, humoral and physical factors. During the last decade, considerable progress has been made in the identification and characterization of these extrinsic renal control systems. Mechanisms intrinsic to the kidney are also important for renal function. These include the autoregulation of blood flow, and the local control of renin secretion. Fundamental questions regarding the mechanism of these intrinsic controls remain unanswered. Recently, endogenous renal adenosine has been claimed to influence the tubuloglomerular feedback control and renin release. Two subclasses of adenosine receptors $A_1{\;}and{\;}A_2$ have been described. The present experiment was carried out to evaluate the effects of $N_6-cyclohexyladenosine$$(CHA,{\;}A_1{\;}selective)$ and 5'-N-ethylcarbox-amide adenosine $(NECA,{\;}A_2{\;}selective)$ on the renal function and renin release in the unanesthetized rabbit. Intra-renal arterial infusion of NECA $(0.3{\sim}10.0n{\;}mole/min/rabbit)$ or CHA $(0.03{\sim}10.0n{\;}mole/min/rabbit)$ caused a prompt and dose-dependent decrease in urine volume, glomerular filtration rate (GFR), renal plasma flow (RPF), filtration fraction (FF), electrolyte excretion and free water clearance $(CH_2O)$, the effect being much more profound with CHA than with NECA. The NECA infusion resulted in a profound decrease of systemic blood pressure, but the CHA infusion did not. Both NECA and GHA infusions caused a prompt and dose-dependent decrease in renin secretion rate, again the effect being greater with CHA than with NEGA. These results suggest that both $A_1{\;}and{\;}A_2$ adenosine receptors may be involved in the intrinsic control of renal function and renin release, and that the $A_1$ receptors plays a more important role than the $A_2$ receptor in the regulation of renal fnction.
The purpose of the present experiment was to determine the functional subclassification of renal adenosine receptor fer the hemdynamic, excretory and secretory functions in unanesthetized rabbits. Adenosine antagonist, 8-phenyltheophylline (8-PT) or theophylline, was infused into the left renal artery followed by an infusion of adenosine agonist, cyclohexyladenosine (CHA) or 5'-N-ethylcarboxamidoadenosine (NECA). Intrarenal arterial infusion of CHA or NECA caused decreases in urine volume, glomerular filtration rate, renal plasma flow and excreted amount of electrolytes and renin release in a dose-dependent manner. Dose-response curves in renal function by CHA or NECA was similar and shifted to the right with pretreatment of 8-PT or theophylline. No significant differences in renal response to CHA and NECA in antagonist-treated rabbits were observed. However, the decrease in renin secretion rate was not affected by the adminstration of adenosine antagonists. These results suggest that the renal effect of adenosine receptor agonists appears by way of specific adenosine receptor, but which is not functionally subclassified in the rabbit.
This study was performed to investigate the effect of chlorella on cadmium (Cd) toxicity in Cd-administered rats. Sixty male Sprague-Dawley rats (14 week-old) were blocked into 6 groups. Cadmium chloride was given at levels of 0 or 325 mg (Cd: 0, 160 ppm), and chlorella powder at levels of 0, 3 and 5%. Cadmium was accumulated in blood and tissues (liver, kidney and small intestine) in the Cd-exposed groups, while the accumulation of Cd was decreased in the Cd-exposed chlorella groups. Fecal and urinary Cd excretions were remarkably increased in Cd-exposed chlorella groups. Thus, cadmium retention ratio and absorption rate were decreased in the Cd exposed chlorella groups. Urinary and serum creatinine, and creatinine clearance were not changed in experimental animals. In addition, metallothionein (MT) synthesis in tissues was increased by Cd administration. The Cd-exposed chlorella groups indicated lower MT concentration compared to the Cd-exposed groups. Moreover, glomerular filtration rate (GFR) was not changed by dietary chI orella and Cd administration. According to the results above, this study could suggest that Cd toxicity can be alleviated by increasing Cd excretion through feces. Therefore, when exposed to Cd, chlorella is an appropriate source which counteracts heavy metal poisoning, to decrease the damage of tissues by decreasing cadmium absorption.
Background: Acute alcoholic intoxication patients (AAIP) are a common public health problem. The aim of this study was to perform a comprehensive laboratory analysis for these patients to investigate the co-morbid medical problem. Methods: We retrospectively reviewed laboratory findings of AAIP who were transferred to the emergency department (ED) from January 2017 to June 2017. Results: A total of 160 male patients were enrolled. Sixteen patients (16/160, 10.0%) and three patients (3/160, 1.9%) had macrocytic anemia and microcytic anemia, respectively. A total of 33 patients (33/160, 20.6%) showed thrombocytopenia ($<150{\times}10^9/L$). Twelve patients (12/159, 7.5%) showed low serum albumin level (<3.5 g/dL). Three patients (3/160, 1.9%) had chronic kidney disease stages 3-4 based on estimated glomerular filtration rate. Six patients (6/27, 22.2%) had high hemoglobin A1c (HbA1c) level (>7.0%). Positive rates of hepatitis B surface antigen and antiHBs antibody (anti-HBs Ab) were 3.5% (5/141) and 49.0% (68/141), respectively. Conclusion: Patients with AAIP who were transferred to ED had various laboratory abnormalities (anemia, thrombocytopenia, high HbA1c). They had low positive rate of anti-HBs Ab. This might be a public health problem, suggesting the need of hepatitis B virus vaccination program for AAIP. Our data suggest the need of further nationwide studies.
The renal function is under regulatory influence of the central nervous system, mainly through activation of sympathetic nerve to the kidney, and it was recently reported that clonidine, an agonist to ${\alpha}_2$-adrenoceptors, induces diuresis and natriuresis when injected directly into a lateral ventricle of the rabbit brain (i.c.v.). This study was undertaken, therefore, to obtain further information as to the role of the central ${\alpha}_2$-adrenoceptors in regulating renal function, by observing the effects of i.c.v. yohimbine, a specific antagonist of adrenoceptors of ${\alpha}_2$-type, on the rabbit renal function, and to elucidate the mechanism involved in it. With 10 ${\mu}g/kg$ i.c.v. of yohimbine sodium excretion transiently increased along with increasing tendency of urine flow, renal plasma flow and glomerular filtration rate. These responses decreased with increasing doses. With 100 and 300 ${\mu}g/kg$ i.c.v. marked antidiuresis and antinatriuresis as well as profound decreases of renal perfusion and glomerular filtration were noted. Systemic blood pressure transiently increased. In reserpinized rabbits, 100 ${\mu}g/kg$ yohimbine i.c.v. did not produce any significant changes in urine flow, sodium excretion as well as in renal hemodynamics. The pressor response was also abolished. In preparations in which one kidney was denervated and the other left intact as control, i.c.v. yohimbine elicited typical antidiuretic antinatriuretic response in the innervated control kidney, whereas the denervated experimental kidney responded with marked diuresis and increases in excretory rates of sodium and potassium and in osmolar clearance in spite of absence of increased filtration and perfusion . Systemic blood pressure responded as in the normal rabbits. These observations indicate that i.c.v. yohimbine affects renal function in dual ways in opposite directions, the first being the antidiuretic antinatriuretic effects which results from decreased renal perfusion and glomerular filtration due to sympathetic activation and which is predominantly expressed in the normal rabbits, and the second less apparent effect being the diuretic and natriuretic action which is not mediated by nerve pathway but brought about by some humoral mechanism and which is effected by decreased sodium reabsorption in the tubules, possibly of the proximal portion.
The purpose of this study was to investigate the effects of green tea catechin on renal dysfunction and blood presure change in chronic cadmium poisoned rats. Sprague-Dawley male rats weighing 100$\pm$10g were randomly assigned to one normal group and three cadmium poisoned groups. Cadmium groups were classified to catechin free diet(Cd-0C group) 0.25% catechin diet(Cd-0.25C group) and 0.5% catechin diet(Cd-0.5C group) according to the levels of catechin supplement. Animals were raids for 20weeks. Cadmium were supplied as drinking water of 50ppm Cd2+ Morphological changes shown through a light microscope and an electro-microscope revealed the mitochondria and tubule epithelial cell edema in Cd -0C group but they were alleviated in catechin supplementation. The urinary $\beta$2-microglobulin that measured to observe the glomerular injury were higher in Cd-poisoned groups than in normal group but they was lowered by catechin supplementation. Glomerular filtration ratios(GFR) in Cd-poisoned groups were significantly lower than in normal group but that of catechin supplementation group was similar to normal group. This suggested that catechin protected the kidney from the functional damage. Angiotensin converting enzyme(ACE) activity and blood pressure(BP) in Cd-poisoned groups were significantly higher than in normal group. Heart rate was tended to increase in Cd-poisoned groups. The results indicate that green tea catechin supplementation on chronic cadmium-poisoned rats normalized the renal dysfunction and blood pressure system.
A glomerular filtration rate (GFR) study is a test that uses radioactive materials or tracers (radiopharmaceuticals) and a computer to see how well the kidneys are working. Asan Medical Center analyzed and compared data between kidney depth, acquired from kidney donors' CT image and acquired from Gates method's GFR value that are calculated by Tonnesen equation. This study was able to confirm that kidney depth measured from CT image was higher than the Gates Method's GFR value, which was calculated by Tonnessen equation; the direct relationship among pathologic results is confirmed. Particularly, kidney donor whose kidney was at the pelvic area had direct relationship with other clinical results. During the GFR test, it is necessary to confirm the location of kidney has no change with reference of CT image. If kidney depth is manually corrected using CT image when we measures GFR of deformed or horse-shoe kidney, it would be possible to acquire the compatible value which is equivalent to clinical result. There would be a possible issue of appropriateness that whether the applied GFR using CT image's kidney depth has clinical validity. In case of a pediatric patient, the GFR derived from Tonnesen was quiet underestimated while manual method and Gordon stay in normal range. Which results may be correct among them? There have been many reports about kidney depth, to be an accurate index of GFR in children. As one of the study performers, we should contemplate what the best option for pediatric patients would be.
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