The Indonesian Biomedical Journal (Prodia Education and Research Institute)
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Protective Effect of Curcumin on Quality Parameters of Sperm and Testicular Tissue Alterations in Alloxan-induced Diabetic Rats as Animal Model
BACKGROUND: Type one diabetes mellitus (DM) is a multisystem disorder whose effects are observed in the reproductive system. Considering the role of curcumin in lowering blood glucose and enhancing antioxidant defense, this research aimed to determine protective effect of curcumin on quality parameters of sperm and testicular tissue alterations in diabetic rats.METHODS: Forty male Wistar rats were randomly divided into five groups, including control (healthy rats), DM (for diabetic model), and also curcumin-treated diabetic model (DM+CUR)50, DM+CUR100 and DM+CUR150. Diabetes was induced using an intraperitoneal injection of 240 mg/ kg alloxan. Following completion of the test period, all rats were sacrificed, and their testes were removed to assess sperm parameters and histological evaluation. The data was analyzed with one-way ANOVA and Tukey post hoc test. The p<0.05 was set as the significance level.RESULTS: Concentration, total sperm motility (TMot), progressive sperm motility (PMot), average path velocity (VAP), curvilinear velocity (VCL), straight line velocity (VSL) of sperm in DM+CUR100 and DM+CUR150 were significantly increased (p=0.005) compared to the diabetic group. Mean diameter (p=0.004) and thickness of the germline epithelium of testis semeniferous tubules (p=0.005) in DM+CUR100 and DM+CUR150 significantly increased compared to the diabetic group.CONCLUSION: It can be concluded that curcumin plays a protective role in testicular tissue alterations and improves sperm parameters. In this regard, curcumin could be suggested to be one of the natural antioxidants that can improve fertility in diabetic patients.KEYWORDS: diabetes mellitus, curcumin, spermatozoa, testis, rat
Artemisia annua Leaf Extract Increases GLUT-4 Expression in Type 2 Diabetes Mellitus Rat
BACKGROUND: The depletion of glucose transporter 4 (GLUT-4) affects blood glucose level in the type 2 diabetes mellitus (T2DM) patient. Herbals supplementation such as Artemisia annua is known to posses an antidiabetic potency, but its effect on long term glucose control marker, glicated hemoglobin (HbA1C) and muscle GLUT-4 expression still has not been investigated.METHODS: Twenty Wistar rats were divided into four groups (five rats per group). The C1 group was consist of healthy control rats and C2 group was consist of diabetic control rats. Diabetic condition was induced by giving high lard fat diet for 28 days, followed with 30 mg/kgBW of Streptozotocin injection at the 29th day. Meanwhile, T1 and T2 group were consist of diabetic rats, which were supplemented with 50 mg/kgBW and 100 mg/kgBW of Artemisia annua leaf extract, respectively. GLUT-4 expression and HbA1C level were measured at the 14th day post-treatment.RESULTS: The GLUT-4 was expressed 1.8 and two times higher in T1 and T2 group, respectively, compared to C2 group. Meanwhile, HbA1C level in C2 group was two times higher than C1 group (11.95±2.52 compared to 5.61±2.69, p0.05)CONCLUSION: Muscle cell’s GLUT-4 in T1 and T2 group was expressed increasingly and significantly different compared to the C2 group. HbA1C level in T2 was slightly reduced although no significant different compared to C2 group.KEYWORDS: Artemisia annua, GLUT-4, HbA1C, type 2 diabetes mellitu
Subchronic Toxicity of Ethanol Extract of Syzygium polyanthum (Wight) Walp. Leaves on Wistar Rat
BACKGROUND: Previous works indicated various pharmacology activities of bay plant (Syzygium polyanthum (Wight) Walp.), however only few studies investigated its toxicity. This work was aimed to study the subchronic toxicity of ethanol extract of this plant.METHODS: White Wistar rats were divided into 4 groups and were treated with 2% of Arabic gum (PGA) suspension, 1000 mg/kg of body weight (BW), 400 mg/kg of BW and 100 mg/kg of BW, respectively. The animals were observed on their body weight, hematology, clinical biochemistry parameters, organ index and histopathology.RESULTS: Flavonoids, tannins, polyphenols, saponins, quinones, monoterpenes and sesquiterpenes were detected in dried leaves and ethanol extract of bay plant. An increase of body weight in male and female groups treated with dose 100 and 400 mg/kg BW compared to controls, was observed. Moreover, there was an increase of white blood cell (WBC) in male and female groups treated with S. polyanthum extracts compared to controls, whereas a decrease of red blood cell (RBC) was observed in male groups treated with S. polyanthum extracts in dose-dependent manner compared to control. No significant changes of RBC were seen in female groups, haemoglobin values were not altered by extract treatment. Photomicrographs of liver, kidney, lungs, heart and spleen histopathology of male and female S. polyanthum extract-treated groups showed no significant alteration compared to controls.CONCLUSION: Our study revealed that S. polyanthum extracts does not show toxicity on the body weight, hematology, creatinine and serum glutamic pyruvic transaminase (SGPT), but fatty liver and necrosis are observed in female rats. This result can be beneficial for plant-based drug discovery, particularly this study provides information about the safety of S. polyanthum to be further developed as candidate of phytopharmaceutics.KEYWORDS: bay plants, salam leaves, hepatotoxicity, necrosis, SGOT, SGP
Relationship between Circulating Protein p53 and High Sensitivity C-Reactive Protein in Central Obesity Men with Inflammaging
BACKGROUND: The mechanism of aging goes along with age, one of which is characterized by cellular senescent, which occurs mostly in adipose tissue. Adipose tissue is the site of accumulation of large cell senescent, in the regulation of obesity and aging. Proteins p53 is marker for cell senescent, which are also known to induce inflammation. This study was aimed to determine the relationship between circulating protein p53 and high sensitivity C-reactive protein (hsCRP) in central obese men with inflammaging.METHODS: The study design is an observational study with cross-sectional approach. The subjects were 75 central obese men (waist circumference/WC > 90 cm), aged ≥ 45 years old. Subjects were divided into 2 age groups, those are middle age group: 45-59 years old (50.7%) and elderly group: ≥ 60 years old (49.3%). Examination of circulating p53 was done using enzyme-linked immunosorbent assay (ELISA) method, and the hsCRP examination was done by chemiluminescent method.RESULTS: It was found that there was a correlation between circulating p53 and hsCRP in elderly (r=-0.414; p<0.05) but not in middle age (r=-0.127; p=0.449).CONCLUSION: From this study, it is assumed that more senescence cells in elderly are resulting in increased chronic inflammation.KEYWORDS: aging, senescent, inflammaging, protein p53, hsCR
N-Acetyltransferase 2 (NAT2) Acetylator Status among Systemic Lupus Erythematosus Patients from A Tuberculosis Endemic Area in Bandung, Indonesia
BACKGROUND: Systemic lupus erythematosus (SLE) patients living in Indonesia are prone to tuberculosis (TB) infection, since this country ranks second globally for TB prevalence. Isoniazid, an anti-tuberculosis (TB) drug, is metabolized by enzyme N-acetyltransferase 2 (NAT2) that is encoded by NAT2 gene. NAT2 haplotype, referring as acetylator status, may predispose as genetic factor in SLE development or complicate SLE therapy. This study explored the NAT2 haplotypes and acetylator status among SLE patients living in a TB endemic area.METHODS: Genomic DNA of 260 registered SLE patients at The Rheumatology Clinic of Dr. Hasan Sadikin General Hospital, Bandung, Indonesia were isolated. NAT2 gene was amplified and sequenced, then NAT2 haplotypes and the acetylator status among SLE patients with or without TB history were determined and presented.RESULTS: Most of SLE patients registered were female (n=250; 96.2%). The median age of patients when SLE was diagnosed for the first time was 27 years old (8-69 years), with organ involvement predominantly in musculoskeletal (80.8%) and mucocutaneous (73.1%). TB history, mostly pulmonary TB, was present in 23.1% of SLE patients of whom TB was diagnosed before SLE (10.4%) or after SLE (10.7%) or both before and after SLE (2%). The acetylator status was mostly intermediate (61.5%) with the NAT2*4/*6B was the most prevalent haplotype (25.8%).CONCLUSION: There is a high number of intermediate and low acetylator status among SLE patients. Since these SLE patients live in TB endemic area, the NAT2 acetylator status determination among SLE patients before starting TB therapy may have clinical benefit to decrease a possible drug induced liver injury, and this warrants further study.KEYWORDS: NAT2, acetylator, systemic lupus erythematosus, tuberculosi
In Vitro Antidiabetic and Antioxidant Activities of Aqueous Extract from the Leaf and Fruit of Psidium guajava L.
BACKGROUND: The leaf and fruit of Psidium guajava L. are potential for neutraceutical beverage especially for antidiabetic drink. The aims of this study were to determine the antidiabetic activity of aqueous extract of leaf (LE) and fruit (FE) from P. guajava.METHODS: Both extracts were investigated for their inhibitory effect on α-glucosidase activity in vitro. Their antioxidant activities were measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging, ferrous ion chelating, reducing power and phosphomolybdate methods.RESULTS: The IC50 of LE, FEandacarbose as a positive control were 5.67, 428.00 and 823.99 μg/mL, respectively. The enzyme kinetic analysis indicated that LE inhibited α-glucosidase in a competitive inhibition type, similar to that of acarbose. Both extracts showed antioxidant activities, with LE showed stronger activities than FE in all methods. In DPPH method, IC50 of LE and FE were 74.77 and 843.84 μg/mL respectively, compared to 53.24 and 21.36 μg/mL for reference antioxidants butylated hydroxytoluene (BHT) and ascorbic acid (AA), respectively. In ferrous ion chelating activity, the IC50 were 147.07 and 2105.05 μg/mL for LE and FE, whereas ethylenediaminetetraacetic acid (EDTA) as a control sample was 66.50 μg/mL. In reducing power and phosphomolybdate methods, at different concentrations, the activities of LE, FE, and standard compounds showed the following order: AA > BHT > LE > FE.CONCLUSION: LE from P. guajava exhibited excellent inhibitory activity against α-glucosidase. In addition, LE had better antioxidant acivities than FE. This study can recommend the aqueous extract from P. guajava as a promising candidate for neutraceutical drink for prediabetic and diabetic patients.KEYWORDS: antioxidant, aqueous extract, α-glucosidase inhibition, guava, Psidium guajava L
Lymphocyte Proliferation Kinetics in Inhabitant of Takandeang Village, Mamuju: A High Background Radiation Areas in Indonesia
BACKGROUND: Mamuju area in West Sulawesi considered as the high natural background radiation area in Indonesia. Our previous study showed that the mean mitotic index (MI) and nuclear division index (NDI) in lymphocytes of Botteng Village, Mamuju inhabitants was lower compared to control samples. To validate our previous study results, here in this study the evaluation of cell proliferation markers which were MI and NDI in peripheral blood lymphocytes (PBL) of Takandeang Village inhabitants was conducted.METHODS: A total 60 people were enrolled in this study, consisted of 35 samples from Takandeang Sub-Village and 25 from normal background radiation area. MI was calculated manually and automatically using Metafer 3.11.2 imaging system. The NDI defined as proportion of mononucleated, binucleated, trinucleated and tetranucleated cells were conducted using cytokinesis block micronucleus (CBMN) assay.RESULTS: The results of this study showed that the mean manual MI in Takandeang Sub-Village inhabitants was lower compared to control group (4.96±2.25 vs. 5.93±2.14). In contrast, the mean automatic MI (20.37±10.49 vs. 18.87±7.49) and NDI (1.555±0.174 vs. 1.523±0.112) in Takandeang Sub-Village inhabitants was higher compared to the control group. Statistical analysis revealed that the difference of mean manual MI, automatic MI and NDI in Takandeang Sub-Village inhabitants was not significantly different compared to the control group(p>0.05).CONCLUSION: It can be concluded that based on this study the chronic low radiation dose exposure in Takandeang Sub-Village, Mamuju has no significant effect on the lymphocytes proliferation.KEYWORDS: lymphocytes, mitotic index, nuclear division index, high background radiatio
Phylogeny of HPV-16 and HPV-18 Multiple Infection of a Patient with Cervical Cancer from Dr. Hasan Sadikin General Hospital, Bandung: A Case Report
BACKGROUND: From all of human papillomaviruses (HPV) genotypes capable of causing cervical cancer, it is estimated that 70 percent are HPV-16 and HPV-18. HPV-16 can infect the tissues in single infection or together with other high-risk types of HPV, and the most common is with HPV-18. The origin of HPV can be identified by its phylogenetic tree. The aim of this study was to determine the phylogeny of HPV-16 and HPV-18 multiple infection in cervical cancer, whether both HPVs were from the same origin.METHODS: Cervical tissue biopsies (n=33) were obtained from Hasan Sadikin Hospital in the period of September to November 2016. HPV genotyping test was performed to confirm the HPV-16 and HPV-18 multiple infection. L1 gene of both HPV-16 and HPV-18 were sequenced for phylogenetic analysis.RESULTS: Phylogenetic analysis of L1 HPV-16 and HPV-18 showed the closest relationship with sequence from China and Thailand, respectively.CONCLUSION: HPV-16 and HPV-18 multiple infection of a cervical cancer patient from Dr. Hasan Sadikin General Hospital Bandung showed a very close L1 phylogeny relationship with isolate from Asian region.KEYWORDS: HPV-16, HPV-18, multiple infection, cervical cancer, Bandun
Distribution of rs1801279 and rs1799930 Polymorphisms in NAT2 Gene among Population in Kupang, Nusa Tenggara Timur, Indonesia
BACKGROUND: N-acetyltransferase-2 (NAT2) enzyme, encoded by NAT2 gene, plays a key role in metabolism of anti-tuberculosis (TB) drug isoniazid. Polymorphisms in NAT2 gene may result in different responses to TB therapy. Since TB prevalence in the eastern part of Indonesia is high, the aim of this study is to explore the distribution of NAT2 gene polymorphisms among population from Kupang, Nusa Tenggara Timur.METHODS: A total of 234 respondents were included from Kupang in 2012. Polymorphisms of NAT2 gene were examined using mass screening platform and the genotypes distribution were presented in percentage. To confirm NAT2 gene polymorphisms, polymerase chain reaction (PCR)-sequencing was performed in a subset of population.RESULTS: The polymorphisms of NAT2 gene showed that the distribution of rs1801279 for GG genotype was 100%; whereas the genotype distribution of rs1799930 for GG, GA and AA was 57%, 35.1% and 7.9%, respectively. In a subset of individuals (n13), acetylator status was well determined by PCR-sequencing, resulting in individual with wild type fast acetylator (NAT2*4; n4), intermediate (NAT2*4/*5 or NAT2*4/*6 or NAT2*4/*7; n7) and poor acetylators (NAT2*6/*6 or NAT2*7/*7; n2).CONCLUSION: The amino acid change in rs1799930 result in intermediate and poor acetylator status in Kupang population. This may lead to suboptimal response of TB therapy. Assessing acetylator status before TB therapy is important and may serve as personalized INH therapy.KEYWORDS: NAT2 gene, polymorphism, acetylator status, Kupan
Antidiabetic Activities of Muntingia Calabura L. Leaves Water Extract in Type 2 Diabetes Mellitus Animal Models
BACKGROUND: Diabetes Mellitus (DM) is a heterogeneous group of disorders characterized by increasing blood glucose levels caused by insufficiency of insulin hormone production and activities. There are significant increases in DM case every year in Indonesia, as a consequent, alternative and better drug is needed to be developed. One of the plants that were often used as traditional medicine for DM in Indonesia was Muntingia carabula L. (kersen) leaf. The aim of this research was to evaluate the antidiabetes activity of M. carabula leaves.METHODS: This study was conducted in vivo by evaluating the antidiabetic activity of M. carabula leaf water extract on two animal models, those are insulin deficiency and insulin resistant model animal. The insulin deficiency animal model was developed by aloxan administration at dose of 50 mg/Kg body weight (bw) intravenously. While the insulin resistance animal model was developed by lipid emulsion administration at dose of 0.42 mL/20 grams bw orally. Both groups were randomly devided into 6 groups, which are negative control group, positive control group, standard drug group (glybenclamide 0.65 mg/Kg bw or metformin 135 mg/Kg bw), and extract groups at dose of 100, 200 and 400 mg/Kg bw. Parameters which were evaluated are fasting blood glucose (FBG) levels for insulin deficiency models and values of constant of insulin tolerance (KITT) for insulin resistant models.RESULTS: In insulin deficient model group, administration of glibenclamide lower the FBG by 43%, furthermore, the extract of M. calabura at doses of 100, 200 and 400 mg/Kg bw also lower the FBG by 13%, 22% and 29%, subsequently. In insulin resistant models, metformin increased the value of KITT from less than 0.5 to 2.91, and administration of the extract at doses of 400, 200 and 100 mg/Kg bw also increased the KITT value to 2.31, 1.57, 1.13, respectively.CONCLUSION: The conclusion was M. carabula leaves water extract with dose of 400 mg/Kg bw had the antidiabetic activities with mechanisms to lower blood glucose level, regenerate pancreatic β cells, and increase insulin sensitivity.KEYWORDS: diabetes mellitus, kersen leaves, Muntingia calabura L., insulin deficiency, insulin resistanc