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1.
Malaysian Journal of Medicine and Health Sciences ; : 23-29, 2022.
Article in English | WPRIM | ID: wpr-987066

ABSTRACT

@#Introduction: Myofibroblast formation in the interstitial area is the hallmark of chronic kidney disease (CKD). Endothelin signalling has been known to play role in physiology and pathophysiology in the kidney. Vitamin D has a reno-protective effect through inhibiting inflammation and fibrosis. However, the interaction between vitamin D and endothelin signalling in the CKD model has not been elucidated yet. Therefore, we aimed to check the difference impact of endothelin (ET) receptor in CKD. Methods: Sprague Dawley rats (3-months-old, 150-250grams) underwent 5/6 subtotal nephrectomy (SN) to induce CKD. Then, it was divided into 4 groups (each contains 6 rats): sham operation (SO), 5/6 subtotal nephrectomy (SN), calcitriol groups (0.01µg/100grBW/day (SN-D1), and 0.05µg/100grBW/day (SN-D2). Calcitriol was administered for 14 days after the surgery. The Sham Operation (SO) group was injected with NaCl. At the specified date, the rats were sacrificed and the kidneys were harvested. Fibrosis was quantified based on Sirius Red staining. Immunostaining was done for localizing fibroblast (PDGFRβ). The mRNA expressions of prepro-ET-1, endothelin receptor A (ETAR), endothelin receptor B (ETBR), and endothelial nitrite oxide synthase (eNOS) were quantified using reverse-transcriptase PCR (RT-PCR). Results: The CKD promotes an elevation of prepro-ET-1, ETBR, and eNOS, and reduction of ETAR (p<0.05) mRNA expression compared to the SO group. Administration of calcitriol (SN-D1 and SN-D2) showed the vice versa effects. However, only SN-D2 group consistently showed statistically significant differences whenever compared to either SO or SN groups. Conclusion: Calcitriol might attenuate interstitial fibrosis in CKD model via ET-1/eNOS signalling.

2.
Malaysian Journal of Medicine and Health Sciences ; : 85-91, 2022.
Article in English | WPRIM | ID: wpr-980410

ABSTRACT

@#Introduction: Chronic kidney disease (CKD) is characterized by fibroblast activation, myofibroblast formation, and up-regulation of transforming growth factor-β1 (TGF-β1) that may activate Snail in fibroblast to myofibroblast transition. Ethanol extract of Yacon leaves is known to have a renoprotective effect on diabetic nephropathy but its effect in the CKD model is unknown. This experimental study aimed to elucidate the effect of ethanol extract from Yacon leaves in attenuating renal failure in a CKD mice model. Methods: Male Swiss-Webster mice (3 months, 30–40 grams, n=25) underwent 5/6 subtotal nephrectomy (SN) to induce CKD. The mice were divided into five groups: SN, SN mice with oral treatment of Yacon leaves ethanol extract with doses 0.735 μg/kg (SN+YK1), 1.47 μg/kg (SN+YK2), and 2.94 μg/kg (SN+YK3), and a Sham operation (SO) group with aquadest 0.1% supplementation. Mice were euthanized on day 14 after the operation and kidneys were harvested. Paraffin sections were used for histological analysis. Immunostaining was done for quantifying fibroblasts and myofibroblasts. We performed RT-PCR to measure TGF-β1 and Snail mRNA expressions. Results: The SN group had significantly higher fibroblast number, myofibroblast fraction area, TGF-β1 and Snail mRNA expressions compared to the SO. The fibroblasts number (p<0.001) and myofibroblast fraction areas (p<0.001) were significantly lower in Yacon treated-groups compared to the SN group. RT-PCR analysis showed lower mRNA expressions of TGF-β1 and Snail, but no significant differences were found among the various Yacon treated-groups. Conclusion: Ethanol extracts of Yacon leaves improved kidney damage in male mice with 5/6 subtotal nephrectomy model.

3.
The Medical Journal of Malaysia ; : 87-92, 2021.
Article in English | WPRIM | ID: wpr-877044

ABSTRACT

@#Introduction: Diabetes mellitus (DM) leads to microvascular injury development and produces diabetes nephropathy (DN) with proteinuria, tubular injury, apoptosis and autophagy with upregulation of Bax, BASP and mTORC-1. Megalin, Cubilin and Neutrophil Gelatinase Associated Lipocalin (NGAL) play role in acute pathological condition of kidney injury, however its expression in chronic and slowly progressive kidney injury such as DN has not been elucidated yet. This study focuses upregulation of Megalin, Cubilin and NGAL in association with tubular injury and apoptosis in DN condition. Materials and methods: Diabetic condition was performed with intraperitoneal injection of Streptozotocin 60 mg/kg body weight (BW) in Sprague Dawley rats (2 months old, n=24), and were kept for 1, 2, and 4 months (DM1, DM2, and DM4, respectively). Control group was injected with NaCl 0.9%. Serum glucose level and proteinuria score were assessed, furthermore tubular injury score was quantified based on Periodic-Acid Schiff (PAS) staining. Reverse Transcriptase-PCR (RT-PCR) was carried out for NGAL, Megalin, Cubilin, m-TOR, Bax, and BASP-1 mRNA expression. Data were analyzed using SPSS 22 software. Results: DM led to kidney injury in this model with significant higher glucose level, proteinuria and tubular injury, especially in DM4 group which represented chronic phase of DN and CKD. These findings associated with upregulation of Megalin,Cubilin and NGAL mRNA expression in DM groups, especially in DM4 group. DM4 group also revealed higher expression of Bax, BASP and mTOR mRNA expression which demonstrated apoptosis. Conclusion: Megalin, Cubilin and NGAL upregulation may represent tubular injury and apoptosis as progression of DN.

4.
Malaysian Journal of Medicine and Health Sciences ; : 162-165, 2021.
Article in English | WPRIM | ID: wpr-979138

ABSTRACT

@#Introduction: Obesity has been demonstrated to induce oxidative stress and inflammation processes that lead to senescence in brain cells. Obesity-induced cellular senescence in the brain is still widely investigated. This study aimed to investigate the expression of antioxidant and neuronal markers in the frontal lobes of obese rats. Methods: Eighteen adult rat Sprague Dawley divided into three groups: Control (SO), Obese-2 (DIO2), and Obese-4 (DIO4) were observed. Control rats were fed with a standard diet AIN 76A for two month. In contrast, DIO2 and DIO4 rats were fed with a high-fat diet daily for two and four months, respectively. After being sacrificed, the rats’ brains were dissected out then the frontal lobes were used for RNA extraction. Reverse transcriptase PCR of SOD2, GPx, BDNF, NeuN and beta-actin was performed to investigate the relative expression of the antioxidant and neuronal markers. Results: DIO2 and DIO4 groups had significantly increased body Weights, blood glucose level and triglyceride level after being fed with a high-fat diet for two and four months, respectively. The DIO4 group had the significantly lowest mRNA expressions of SOD2, GPx, BDNF and NeuN. Conclusion: Decreased antioxidant and neuronal markers in the rats frontal lobes were observed as the chronic effect of obesity.

5.
Malaysian Journal of Medicine and Health Sciences ; : 94-100, 2020.
Article in English | WPRIM | ID: wpr-843064

ABSTRACT

@#Introduction: Chronic kidney disease (CKD) leads to tubular injury, kidney fibrosis and anemia. These conditions are influenced by fibrotic and anti-fibrotic substances, such as Transforming Growth Factor beta-1 (TGF-β1), Hepatic Growth Factor (HGF), and Bone Morphogenic Protein-7 (BMP-7). Yacon is an herbal medicine which has not been elucidated in CKD. This study aimed to investigate the effect of ethanolic extract of Yacon leaves on attenuating renal injury in CKD model in mice. Methods: We performed 5/6 subtotal nephrectomy (SN) in male Swiss-Webster mice (3 months old, 30–40 grams) to induce chronic kidney disease, then the mice were sacrificed at day 14. The mice (n=25) were divided into five groups: one SN group, three groups of SN with administration of Yacon extract, and one group of sham operation (SO, with supplementation of 0.1% aquadest). There were three different doses of ethanolic extract of Yacon leaves: 98 mg/kg BW (SN+YK1), 49 mg/kg BW (SN+YK2), and 24.5 BW mg/kg (SN+YK3). Tubular injury, perivascular and interstitial fibrosis were quantified based on histopathological examination. Reverse-transcriptase PCR (RT-PCR) was performed to quantify HGF and BMP-7. Results: SN group demonstrated CKD with elevation of creatinine level, anemia, tubular injury, glomerulosclerosis, and fibrosis. Yacon extract treatment showed attenuation of injury with lower creatinine level, tubular injury, glomerulosclerosis and fibrosis compared to the SN group. HGF and BMP-7 mRNA expressions were higher in Yacon-treated groups than the SN group. Conclusion: Yacon treatment might ameliorate CKD through reducing fibrosis and increasing expression of anti-fibrotic genes.

6.
Malaysian Journal of Medicine and Health Sciences ; : 82-85, 2020.
Article in English | WPRIM | ID: wpr-843062

ABSTRACT

@#Introduction: Chronic Kidney Diseases (CKD) leads to kidney fibrosis which characterized by tubular injury and atrophy with interstitial fibrosis. Endothelin-1 (ET-1) and endothelial Nitrite Oxide Synthase (eNOS) are known to play role in CKD and kidney fibrosis, although their correlation with tubulo-interstitial injury have not been understood clearly. Methods: 5/6 Subtotal Nephrectomy (SN) was performed in male Swiss Background mice to induce CKD. Sham operation (SO, n=5) procedure was performed on mice as control. The mice were sacrificed in day 7 (1N, n=5) and day 28 (4N, n=5) after operation. We measured creatinine serum to assess renal function. Tubular injury score was quantified based on Periodic-Acid Schiff (PAS) staining. Prepro-ET-1 and eNOS were quantified using RT-PCR. Results: SN_1N and SN_4N groups had significant higher of serum creatinine and tubular injury from SO group. Densitometry analysis of RT-PCR revealed up-regulation of prepro-ET-1 mRNA expression in SN_1N and SN_4N (p<0.05 vs SO). Meanwhile, we found a significant increase of eNOS expression in SN_1N, and then it reduced significantly in SN_4N. We found significant parallel correlation between ET-1 and tubular injury expression (r: 0.768;p<0,05), meanwhile there were insignificant inverse correlation between eNOS and tubular injury (r: -0.354;p>0.05). Conclusion: eNOS might play role as a counterbalance in the up regulation of ET-1 in acute condition after SN. However, it failed in chronic condition. These lead to deterioration of renal function and tubular injury. An imbalance between ET-1 and eNOS expression in chronic CKD model might play role in profound renal damage.

7.
Malaysian Journal of Medicine and Health Sciences ; : 71-77, 2020.
Article in English | WPRIM | ID: wpr-843060

ABSTRACT

@#Introduction: Kidney ischemic-reperfusion injury (IRI) is the main cause of acute kidney injury (AKI) which leads to the inflammation epithelial apoptosis and interstitial fibrosis as the chronic consequenses. Centella asiatica (CeA) has been known to have various pharmacological effects such as, anti-inflammatory, antioxidant, anti-fibrosis, and, anti-apoptosis. We aimed to elucidate the role of CeA in inhibiting kidney injury and infammatory mediators due to kidney IRI. Methods: Kidney IRI were performed with bilateral renal pedicles clamping in Swiss background mice (3 months-old, 30-40 grams) for 30 minutes (IR group, n=6), then terminated at day 7 after operation. At the next day, the mice that have been underwent bilateral kidney IRI were administered per-orally with ethanolic extract of CeA (210 mg/kg of BW, CeA1 group, n=6, and 420 mg/kg of BW, CeA2 group, n=6). The Sham Operation (SO group, n=6) was used as control. At the day 7 after the surgery, the mice were sacrificed and the kidneys were harvested. The kidney was used to assess tubular injury, interstitial fibrosis, and macrophage number, and another kidney was used to assess the mRNA expression of TLR4. Data were quantified using SPSS 22. Results: Kidney IRI produced significantly higher tubular injury, interstitial fibrosis and macrophage number (p<0.05) compared to SO with upregulating TLR4 mRNA expression (p<0.05). CeA treatment attenuated the tubular injury, interstitial fibrosis, macrophage number, and TLR4 mRNA expression which obviously shown in higher-dose of CeA (p<0.05). Conclusion: CeA ameliorates tubular injury, kidney fibrosis, and inflammatory mediators due to kidney IRI.

8.
Malaysian Journal of Medicine and Health Sciences ; : 62-66, 2020.
Article in English | WPRIM | ID: wpr-843058

ABSTRACT

@#Introduction: Obesity has been demonstrated to induce oxidative stress and inflammation processes that lead to senescence. Obesity-induced cellular senescence in the brain is still widely investigated. This study aimed to investigate the expression of senescence markers in the frontal lobes of obese rats. Methods: Three groups of rats: control, Obese-2 (Ob-2), and Obese-4 (Ob-4) were observed. Control rats were fed with a standard diet for one month. In contrast, Ob-2 and Ob-4 rats were fed with a high-fat diet daily for two and four months, respectively. After being sacrificed, the rats’ brains were dissected out then the frontal lobes were used for RNA extraction. Reverse transcriptase PCR of p-16, p-21, and beta-actin was performed to investigate the relative expression of the senescence markers. Results: Ob-2 and Ob-4 groups had significantly increased body weight after being fed with a high-fat diet for two and four months, respectively. The mRNA expressions of p-16 and p-21 in the frontal lobes of three groups showed similar patterns. The ob-4 group had the highest mRNA expressions of both p-16 and p-21. In comparison to control and Ob-2 groups, the mRNA expressions of p-16 and p-21 were markedly increased. Furthermore, the mRNA expressions of p-16 and p-21 between control and Ob-2 groups were comparable. Conclusion: Increased senescence markers in the rats’ frontal lobes were observed as the chronic effect of obesity.

9.
Malaysian Journal of Medicine and Health Sciences ; : 49-55, 2020.
Article in English | WPRIM | ID: wpr-843056

ABSTRACT

@#Introduction: Uric acid is a common cause of liver tissue damage due to its hepatotoxic effect. This study is aimed to investigate: (1) the effect of uric acid on liver damage which can be seen from the serum levels of SGOT and SGPT, (2) the inflammatory response demonstrated by TLR-4 and MCP-1 mRNA expression, and (3) the proportion of hepatocytes apoptosis in mice. Methods: A total of 25 adult male Swiss-Webster mice were divided into five groups: one control group and four uric acid groups (AU7, AU14, AU21 and AU28). The uric acid groups were administered with 125 mg/kgBW uric acid for 7, 14, 21, and 28 days. Following the treatment, mice were terminated and the liver was harvested. Blood sample was taken from retro-orbital vein to assess serum uric acid, SGOT, and SGPT levels. RT-PCR was performed to examine the mRNA expressions of TLR-4 and MCP-1. TUNEL staining was used to assess the proportion of apoptotic hepatocytes. Results: Induction of uric acid caused hyperuricemia, increased expression of TLR-4 and MCP-1 mRNA significantly (p<0.05) which indicated an inflammatory reaction. The levels of SGOT and SGPT were elevated significantly (p<0.05), as well as the number of hepatocyte apoptosis (p<0.05). Conclusion: Hyperuricemia affected the inflammatory response by increasing the mRNA expression of TLR-4 and MCP-1. An increased number of apoptotic hepatocytes was likely caused by the ongoing inflammatory reaction during the induction of uric acid.

10.
Malaysian Journal of Medical Sciences ; : 37-44, 2020.
Article in English | WPRIM | ID: wpr-825498

ABSTRACT

@#Background: Cellular senescence may play a role in the development of kidney fibrosis, but its specific association with apoptosis or proliferation have yet to be determined. Objectives: This study aims to determine the effects of unilateral ureteral obstruction (UUO) on proliferation, cellular senescence and apoptosis in kidney fibrosis. Methods: A unilateral ureteral obstruction (UUO) procedure was performed to induce kidney fibrosis in 24 Swiss mice (3 months old, 30 g–40 g). Mice were sacrificed on day 3 (UUO3, n = 6), day 7 (UUO7, n = 6) and day 14 (UUO14, n = 6). Sham operation (SO) procedures were performed on the control group. The expression of Bcl-2, p16 and Bax mRNA was quantified with reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemical (IHC) staining with anti-Bcl-2 and p53 antibodies was used to determine the localisation of proliferation and apoptosis. Data were analysed using one-way ANOVA followed by a post hoc least significant difference (LSD) test (P < 0.05) Results: RT-PCR analysis showed higher mRNA expression of Bcl-2, p16 and Bax in the UUO groups compared with SO group (P < 0.05). Immunostaining showed that Bcl-2 and p53 expression in tubular epithelium in the UUO groups, except Bcl-2 expression was found in interstitial areas of UUO14 group. Conclusion: Senescence in UUO might be associated with epithelial apoptosis and myofibroblast proliferation.

11.
Malaysian Journal of Medical Sciences ; : 53-63, 2019.
Article in English | WPRIM | ID: wpr-780798

ABSTRACT

@#Background: Chronic kidney disease (CKD) leads to inflammation, fibrosis and destruction of the renal architecture. Centella asiatica (CeA) is an herbaceous plant with antiinflammatory effects. We aimed to elucidate the effect of CeA on inflammation, fibrosis, vascular remodelling and antifibrotic substances in a 5/6 subtotal nephrectomy (SN) model in mice. Methods: Mice were divided into three groups: sham operation (SO, n = 6), 5/6 SN for seven days (SN7, n = 7) and SN7 with oral CeA treatment (SN7-CeA, n = 7). At day 7, mice were euthanised, kidneys were harvested and stained with periodic-acid Schiff (for tubular injury and glomerulosclerosis) and sirius red (for fibrosis and vascular remodeling) staining. mRNA expression of prepro-endothelin-1, nephrin, E-cadherin, bone morphogenic protein-7 (BMP-7), toll-like receptor 4 (TLR4), tumour necrosis factor-α (TNFα) and hepatocyte growth factor (HGF) were quantified using reverse transcriptase-PCR. Results: SN group demonstrated significant higher interstitial fibrosis, vascular remodeling, tubular injury and glomerulosclerosis (P < 0.01) compared to SO group. Meanwhile, in SN7-CeA demonstrated attenuation of vascular remodeling as shown by significant higher lumen area with lower Wall/Lumen area ratio compared to SN7. RT-PCR analysis showed up-regulation of nephrin, BMP-7 and E-cadherin mRNA expression (P < 0.05) and down-regulation of ppET-1 in SN7-CeA group compared to SN7 group (P < 0.05). Conclusion: CeA may ameliorate renal injury in the SN model in mice.

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