The Indonesian Biomedical Journal

208-17

Authors: Zaenah Zuhair Alamri, Soliman Mohammed Alfaifi

BACKGROUND: Long-term usage of lithium carbonate (Li2CO3) as treatment of bipolar disorder might cause nephrotoxicity. Li2CO3-induced nephrotoxicity usually treated by renal dialysis, which is quite expensive. Usage of natural products that possess anti-inflammatory and antioxidant properties as biochanin A (BCA) may be useful against Li2CO3 nephrotoxicity. Therefore, this study was conducted to evaluate Li2CO3 nephrotoxic effects and BCA therapeutic and protective effects against it. METHODS: Twenty-eight rats divided into 4 groups: negative control (NC), Li2CO3, Li2CO3 + BCA therapeutic, and BCA + Li2CO3 protective group. Complete blood picture, serum kidney function tests (urea, creatinine, and cystatin C) and kidney tissue homogenate oxidative stress index as malonaldehyde (MDA), superoxide dismutase (SOD), glutathione S-transferase (GST) and catalase (CAT) were measured using enzyme linked immunosorbent assay (ELISA) methods. While, kidney histopathological changes were evaluated under light microscope. RESULTS: Li2CO3 administration elicited significant changes in hematological parameters as hypochromic anemia, decreased platelets and leukocytosis. Serum urea, creatinine and cystatin C were elevated. Renal homogenate analysis revealed significant elevation of MDA and decline in GST, CAT, SOD levels. Kidney histopathology analysis revealed hemorrhage between renal tubules, glomerular capillaries congestion, Bowman’s space dilatation, structural alterations in renal tubules cells include loss of brush border, deeply stained nuclei and elevated in size and number of cytoplasmic vacuoles. Therapeutic and protective groups of BCA showed amelioration of hematological alteration, kidney functions, oxidative stress markers and restoration of kidney tissues. CONCLUSION: BCA has both protective and therapeutic effects against Li2CO3-induced nephrotoxicity possibly through the reduction of oxidative stress.

228-36

Authors: Novi Dewi Tanjung, Nieka Adhara Wahono, Ninik Mudjihartini, Ani Retno Prijanti

BACKGROUND: Zinc released into the synaptic cleft able to modulate various signaling pathways, including brain derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase B (TrkB). Zinc binding to its receptor, G-protein coupled receptor 39 (GPR39), may trigger biochemical pathways leading to cAMP response element binding protein (CREB)-dependent gene transcription that subsequently promotes BDNF upregulation. Therefore, zinc dyshomeostasis should be considered as a condition that induces disruption of CREB/BDNF signaling. This study was conducted to examine the effect of maternal zinc diet on hippocampal expression levels of CREB and BDNF in offspring. METHODS: One-day pregnant rats were randomly divided into five groups: zinc-deficient (D), zinc-restricted (R), zinc-adequate (A), zinc-supplemented (S), and excess zinc-supplemented (ES). The groups had different zinc diets during pregnancy and lactation. The behavioral function of the offspring was tested with Y-maze at the 43th postnatal. Hippocampus was isolated, BDNF was assessed by quantitative real-time polymerase chain reaction (qRT-PCR), and CREB was examined using sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: Spatial working memory measurement demonstrated that D and ES group exhibited a significantly lower spontaneous alternation than other groups. The qRT-PCR and ELISA analysis revealed the hippocampal expression level of BDNF and CREB decreased in groups D and ES, but tended to increase in groups R and S, until the highest expression peak was found in group A. CONCLUSION: High and low intake of zinc induces lower expression of BDNF and CREB in hippocampus, which further impairs learning and memory. Our findings suggest the signaling pathway of CREB/BDNF is involved in zinc dyshomeostasis-induced cognitive impairments.

248-54

Authors: Manuel Hutapea, Syamsudin Syamsudin, Iin Kurnia, Miswar Fattah, Ujang Saeful Hikmat, Vinessa Gracia Putri

BACKGROUND: Tumor markers such as human epididymis protein 4 (HE4), cancer antigen 125 (CA-125), and risk of ovarian malignancy algorithm (ROMA) are frequently utilized for diagnostic and prognostic purposes. Lymphocytes, essential immune cells, play a significant role in eliminating cancer cells. However, the precise correlation between tumor markers and lymphocytes remains incompletely elucidated. The aim of this study was to explore the correlation between tumor markers and lymphocyte subtype profiles in differentiating ovarian cancer and benign tumors. METHODS: This was a cross-sectional study involving 12 ovarian cancer and 17 benign ovarian tumor patients. Blood samples were collected for the characterization of T lymphocytes, B lymphocytes, natural killer (NK), and T regulatory (Treg), which were analyzed using flowcytometry. Additionally, tumor markers HE4 and CA-125 were measured from patient serum using the chemiluminescent microparticle immunoassay (CMIA) method. RESULTS: Benign ovarian tumors and ovarian cancer can be distinguished by a significant increase in HE4 levels (p=0.004), ROMA (p=0.004), and Treg cells (CD4+/CD25+/FOXP3+, p=0.017). Furthermore, the correlation between tumor markers and lymphocytes indicates that an increase in ROMA was weakly correlated with an increase in the percentage of T regulatory cells (CD4+/CD25+/FOXP3+, r=0.553, p=0.006) and B lymphocytes (CD19+, r=0.528, p=0.010), accompanied by a decrease in the number of T lymphocytes (CD3+, r=-0.598, p=0.003), T helper lymphocytes (CD3+CD4+, r=-0.594, p=0.003), and cytotoxic lymphocytes (CD3+CD8+, r=-0.510, p=0.013). CONCLUSION: The elevation of serum tumor markers (HE4 and ROMA) accompanied by an increase in Treg cells can distinguish between benign ovarian tumor patients and ovarian cancer patients.

263-8

Authors: Ida Ayu Ratih Wulansari Manuaba, Ketut Suryana, I Made Bakta, I Made Sudarmaja

BACKGROUND: Early detection and management of lupus nephritis (LN) in systemic lupus erythematosus (SLE) are essential to prevent irreversible kidney damage and improve patient outcomes; therefore, identifying reliable biomarkers to predict LN is paramount. However, there are still relatively few studies examining the potential biomarkers for LN in SLE patients. This study was conducted to investigate serum deoxyribonuclease I (DNase), soluble tumor necrosing factor 1 (sTNFR1) and soluble tumor necrosing factor 2 (sTNFR2) as a risk factor for LN in SLE patients. METHODS: A case-control study involving SLE patients aged 20-60 years was conducted. Blood was withdrawn from each subject for the measurement of serum level of DNase1, sTNFR1, and sTNFR2 that was performed using enzyme-linked immunoassay (ELISA) methods. Data was then analyzed using Chi-Square test and logistic regression tests. RESULTS: A total of 22 patients with LN and 22 without LN were included. The cut-off value for DNase1, sTNFR1, and sTNFR2 were 5.05 ng/mL, 6.52 ng/mL, and 7.02 ng/mL, respectively. The risk factors of LN in SLE patients were the low level of serum DNase1 (aOR=6.64; 95%CI: 1.25-35.29; p=0.026), low level of serum sTNFR1 (aOR=8.12; 95% CI: 1.56-42.10; p=0.013), and low level of serum sTNFR2 (aOR=5.57; 95%CI: 1.03-30.11; p=0.046). CONCLUSION: Serum DNase1 lower than 5.05 ng/mL, sTNFR1 lower than 6.52 ng/mL, and sTNFR2 lower than 7.02 ng/mL were risk factors for lupus nephritis in SLE patients. Hence, serum DNase1, sTNFR1 and sTNFR2 could be used as risk factors predictors for LN in SLE patients.

277-84

Authors: Heri Nugroho, Abdul Mughni, Indra Kusuma Adi Putranto, Anggoro Teguh Prasetya, Vicky Novitasari

BACKGROUND: Diabetes mellitus (DM) is often associated with obesity, which can lead to chronic inflammation. Sleeve gastrectomy (SG) is a common treatment for obesity. Combining SG with omentoplasty, might help reducing inflammation in pancreatic beta cells. However, there is limited research regarding the combined effects of SG and omentoplasty in type 2 DM (T2DM). This study was conducted to fill this gap by evaluating the impact on body weight, insulin resistance, glucagon expression, and levels of interleukins (IL)-1, IL-6, and IL-10 in obese rats with type II DM. METHODS: An experimental study was conducted on 18 obese Wistar rats with DM that were randomized into: control, T1 (SG), and T2 (SG + omentoplasty). SG involved the surgical removal of a portion of the stomach to reduce its size, while omentoplasty utilized the omentum to target inflammation in pancreatic beta cells. Venous blood samples were taken from subjects one day before and ten days after the intervention to measure the biomedical parameters with various methods. Data was statistically analyzed using paired t-tests for pre-test and post-test differences, and Post Hoc tests or Mann-Whitney tests for hypothesis testing. RESULTS: All rats were confirmed to have obesity and DM according to the Lee index and blood glucose levels. T2 group exhibited a significant decrease in body weight, homeostatic model assessment of insulin resistance (HOMA-IR) values were lower, and glucagon expression, IL-1, IL-6, and IL-10 levels were significantly greater compared to both control and T1 groups. CONCLUSION: The combination of SG and omentoplasty significantly improves inflammation and insulin resistance in obese rats with T2DM.