Paraoxonase-1 activities and procalcitonin levels in sepsis and non-infectious systemic inflammatory response syndrome patients in a tertiary intensive care unit

Sepsis and septic shock remain to be a leading cause of death in the intensive care unit (ICU), including in Malaysia. Distinguishing early sepsis from non-infectious systemic inflammatory response syndrome (SIRS) may be difficult upon presentation. Thus, research has been ongoing in finding a specific and effective marker for sepsis, where paraoxonase-1 (PON1) has shown to be a promising contender. PON1 is a high density lipoprotein associated enzyme, where early researches have shown that its activities decrease as oxidative stress increases in intensity during sepsis. This study aimed to compare PON1 activities between sepsis and non-infectious SIRS patients, as well as comparing its activities in patients who ultimately survived or died as a result of their ordeal. In addition, this study looked into the diagnostic and predictive performance of PON1 for sepsis and mortality as well as the correlation between PON1 activities and a known sepsis marker, procalcitonin (PCT). This prospective observational study, recruited ICU patients above the age of 18 with SIRS and divided them into sepsis and non-infectious SIRS based on clinical assessment with or without positive cultures. PON1 activities; paraoxonase (PON) and arylesterase (ARE) activities, and PCT levels were measured daily over the first three days of ICU admission. Out of the 239 patients recruited, 164 (69%) had sepsis and 68 (28.5%) died in hospital. Results showed significantly lower PON1 activities in sepsis compared to non-infectious SIRS throughout the three-day. PON1 activities were also significantly lower in non-survivors compared to the survivors Further analysis also showed that ARE activity to be a slightly better detector of sepsis than PON activity (PON AUC 0.64-0.65 versus ARE AUC 0.67-0.69), but similar in power in predicting mortality (ARE AUC 0.61-0.64, PON AUC 0.62-0.64). PON1 activities and PCT levels were all significantly correlated with weak to moderate correlation with r-values between 0.207- 0.476. We concluded that PON1 activity measured early on ICU admission has a big potential to be a biomarker in distinguishing sepsis from non-infectious SIRS and in prediction of mortality. A larger scale study, involving multiple centres could be done to further confirm or refute these findings

Microarray data analysis to identify differentially expressed genes and biological pathways associated with Tualang Honey supplementation in NASH animal model

Tualang Honey (TH) is a multifloral jungle honey that has been shown to have anti-inflammatory and antioxidant properties. Thus, it has been proposed as a potential supplement in the management of non-alcoholic steatohepatitis (NASH). This study aimed to identify potential key genes and biological process associated with the therapeutic effects of TH in NASH animal model. Twenty Sprague Dawley rats were used in this experiment. Five rats were given standard commercial pellets throughout the experiment and acted as controls. Fifteen rats were subjected to the 12% high-cholesterol diet (HCD) for sixteen weeks to induce NASH. They were then divided into 3 groups, with each group receiving 3 different dosages of TH supplementation for four weeks. RNA was extracted from serum using RNeasy extraction kit (Qiagen) and microarray analysis was performed. A total of 3062 differentially expressed genes (DEGs) were identified including 2788 upregulated genes and 274 downregulated genes in all treated groups. There were 15 genes significantly upregulated including aldehyde dehydrogenase family, cytochrome P450 and nuclear transcription factor. Whilst, 13 genes were significantly downregulated such as apelin, interferon regulatory factor 2 and stearoyl-Coenzyme A. Following pathway enrichment analysis, 34 biological processes were significantly modified (p < 0.05). Among the pathways implicated in the effects of TH were those involved in the inflammatory response, lipid biosynthetic process and cholesterol metabolic process. The present study demonstrated that the DEGs involved in the therapeutic effects of TH were enriched in several pathways and further validation is required to confirm their specific roles

The effects of Tualang honey on sperm profile and follicular-stimulating hormone in high cholesterol diet induced animal model

Introduction: Hypercholesterolaemia is a recognised factor associated with male infertility. However, currently, there is limited therapy available. Tualang honey (TH) is a type of Malaysian polyfloral wild honey produced by the rock bee (Apis dorsata) that has been proven to exert both anti-inflammatory and anti-oxidative effects. This study aimed to determine the effects of TH on the sperm profile and follicular-stimulating hormone (FSH) level of high cholesterol diet (HCD) administered rats. Materials and Methods: Thirty male Sprague Dawley rats were randomly divided into a control group (n=6) fed with the standard diet and HCD group (n=24). The rats in the control group were fed with standard rat pellets while rats in the HCD group were fed with 12% HCD for 16 weeks. At the end of 16 weeks, rats in HCD group were divided into four subgroups (H1, H2, H3, and H4) and continued with 12% HCD in addition to administration of distilled water, 1.2, 2.4, and 3.0 g of honey per kg body weight daily respectively for another 4 weeks. While the rats in the control group continued with commercial rat pellets without honey supplementation for the same duration. At the end of 4 weeks, all rats were sacrificed, and blood specimens were taken for FSH estimation, and the cauda epididymis was collected for sperm analysis. Results: The FSH level and the sperm parameters (sperm concentration, morphology, percentage of total sperm motility,progressive motility, and viability of rats in HCD subgroup H1 were significantly reduced compared to the control (p<0.001). In contrast, all TH supplemented subgroups demonstrated significant improvement in their sperm parameters (p<0.001). The higher the dosage of TH in the HCD subgroup, the greater the improvements in the sperm concentration, morphology, and viability. Although the levels of FSH were increased in all treated HCD groups compared to H1, there was no significant difference in the serum FSH levels between the groups. Conclusion: The Tualang honey supplementation improved the sperm profile in HCD induced animal models

The effects of Tualang honey on sperm profile in high cholesterol diet induction animal model

Background: Hypercholesterolaemia and obesity are recognized factors associated with male infertility. They have been shown to reduce the semen quality, change the sperm proteomes and also contribute to erectile dysfunction. However, currently there is limited therapy available. Tualang honey (TH) is a type of Malaysian polyfloral wild honey produced by the rock bee (Apis dorsata) proven to exert both anti-inflammatory and anti-oxidative effects. Objective: This study aimed to determine the effects of TH on the sperm profile of animal model with chronic exposure to high cholesterol diet. Methodology: Thirty male Sprague Dawley rats 2 weeks of age weighing 200 - 250 gm were divided into two groups, the high (12%) cholesterol diet (12% CD; n= 24) and standard diet (SD; n=6) and were fed for 16 weeks. At 16 weeks, the rats in the 12% CD group were subsequently divided into four groups. The first group was continued with only 12% CD while the other 3 groups in addition to the 12% CD, they were given TH supplement at different doses (1.2, 2.4 and 3.0 g/kg/day) for 4 weeks. Sperm profile analysis from the caudal epididymis was performed for all groups at the end of the 4 weeks. Results: At 16 weeks of 12% CD, the sperm concentration, the percentage of total sperm motility, progressive motility and viability reduced significantly compared to the SD group (p<0.001). On the contrary, all TH supplemented groups demonstrated significant improvement in the sperm concentration, percentage of sperm viability, total sperm motility and progressive motility (p<0.001). Conclusion: TH supplementation of animal model with chronic exposure to high cholesterol diet improved the sperm profile parameters. Based on our findings, there is a need to further explore the potential TH in improving male infertility associated with hypercholesterolaemia and obesity

Lipid profiles changes in 12% high cholesterol diet induced non-alcoholic steatohepatitis animal model following supplementation of Tualang honey and diet modifications

Non-alcoholic steatohepatitis (NASH) is associated with hypercholesterolaemia and hypertriglyceridaemia. The main recommendation for NASH management is a diet prescription to reduce body weight. Tualang honey (TH) has been suggested to improve lipid profiles and hence, may help combat NASH. This study aimed to investigate the effects of TH supplementation coupled with diet modification on lipid profiles of rats given a 12% high cholesterol diet (HCD). Fifteen Sprague Dawley rats were fed with HCD for 16 weeks. They were then divided into 3 groups. Group A rats were not treated and continued HCD (control). Group B rats were supplemented with TH (3.0g/kg) and continued HCD, while group C was given TH (3.0g/kg) but was changed to a normal diet for 4 weeks. Compared to the control (A), group C showed a significantly reduced total cholesterol (2.92 ± 0.78 vs 1.68 ± 0.16 mmol/L, p<0.005), and triglycerides (3.30 ± 0.49 vs 0.98 ± 0.36 mmol/L, p<0.001). Whilst group B only showed a significant reduction in triglyceride (3.30 ± 0.49 vs 2.04 ± 0.80 mmol/L, p<0.003) but no significant changes in total cholesterol. Diet modification in addition to TH supplementation may further enhance the lipid profile modifications of HCD rats as compared to TH alone

Tualang honey supplementation attenuates the lipid profile In high cholesterol diet induced non-alcoholic steatohepatitis animal model

Introduction: Hypercholesterolaemia, insulin resistance and metabolic syndrome are the key features for Non-alcoholic Steatohepatitis (NASH) disease. Non pharmaceutical approaches, particularly nutritional counselling and diet prescription to reduce body weight remains the main recommendation for NASH management. Tualang honey (TH) has been proposed to improve lipid profiles and hence, may be beneficial in NASH management. Objectives: This study aimed to investigate the effects of TH at three different dosages on lipid profiles of rats given 12% high cholesterol diet (HCD). Methodology: Thirty male Sprague Dawley rats were fed with 12% HCD for 16 weeks. After 16 weeks, the rats were divided into four groups. The first group (Group A - control) was given distilled water while the rats in the remaining three groups, were treated with 1.2 g/kg (Group B), 2.4g/kg (Group C) and 3.0g/kg (Group D) doses of TH daily for four consecutive weeks. Rats in all groups were changed to a normal diet during this period. At the end of four weeks of TH treatment, blood samples were collected from the rats via the retro-orbital sinus and lipid profiles were analysed. Results: Compared to the control (Group A), the total cholesterol were reduced in all groups treated with TH (Group B, C and D); 1.84±0.134 vs. 1.52±0.192 vs. 1.62± 0.319 vs. 1.68±0.164 mmol/L respectively. The lowest triglycerides were seen in rats treated with 3.0 g/kg/day of TH; 1.26±0.487 vs. 1.18±0.414 vs. 1.34±0.622 vs. 0.98±0.356 mmol/L (Group A, B, C and D respectively). The LDL/HDL ratio was found to be the lowest in rats treated with 2.4 g/kg/day of TH (Group C). Conclusion: Supplementation of TH in addition to diet prescription may enhance the lipid profile modifications of HCD rats as compared to diet prescription alone, independent of TH dosage

Microarray data analysis to identify differentially expressed genes and biological pathways associated with Tualang Honey supplementation in NASH animal model

Tualang Honey (TH) is a multifloral jungle honey that has been shown to have anti-inflammatory and antioxidant properties. Thus, it has been proposed as a potential supplement in the management of non-alcoholic steatohepatitis (NASH). This study aimed to identify potential key genes and biological process associated with the therapeutic effects of TH in NASH animal model. Twenty Sprague Dawley rats were used in this experiment. Five rats were given standard commercial pellets throughout the experiment and acted as controls. Fifteen rats were subjected to the 12% high-cholesterol diet (HCD) for sixteen weeks to induce NASH. They were then divided into 3 groups, with each group receiving 3 different dosages of TH supplementation for four weeks. RNA was extracted from serum using RNeasy extraction kit (Qiagen) and microarray analysis was performed. A total of 3062 differentially expressed genes (DEGs) were identified including 2788 upregulated genes and 274 downregulated genes in all treated groups. There were 15 genes significantly upregulated including aldehyde dehydrogenase family, cytochrome P450 and nuclear transcription factor. Whilst, 13 genes were significantly downregulated such as apelin, interferon regulatory factor 2 and stearoyl-Coenzyme A. Following pathway enrichment analysis, 34 biological processes were significantly modified (p < 0.05). Among the pathways implicated in the effects of TH were those involved in the inflammatory response, lipid biosynthetic process and cholesterol metabolic process. The present study demonstrated that the DEGs involved in the therapeutic effects of TH were enriched in several pathways and further validation is required to confirm their specific roles

Tualang honey supplementation alleviates obesity and dyslipidaemia in high cholesterol diet induced non-alcoholic steatohepatitis animal model

INTRODUCTION: Dyslipidaemia and obesity are two main features of non-alcoholic steatohepatitis (NASH). This study aimed to investigate the effects of Tualang honey (TH) supplementation on bodyweight, liver weight, and lipid profiles in high cholesterol diet (HCD) induced NASH animal model. MATERIALS AND METHODS: Sixteen Sprague-Dawley rats were given 12% HCD for 16 weeks to induce NASH. These animals were divided into 4 groups; Group 1 (continued HCD), Group 2 (changed to normal diet), Group 3 (normal diet and TH 1.2g/kg) and Group 4 (normal diet and TH 3.0g/kg) for the following 4 weeks. Bodyweight was measured daily. At the end of the study, blood was collected via retro-orbital bleeding and the rats were sacrificed to harvest their liver. RESULTS: The group 4 rats had significantly lower mean final bodyweight than rats in group 1, 2 and 3 (478.0±24.4 vs. 641.5±25.1, 593.8 ±29.3, 552.0±72.9 g, p<0.05). Animals in group 4 were also found to have a significantly lower mean liver weight compared to groups 1 and 2 (12.9±0.9 vs 20.1±2.2, 15.7±1.2 g, p<0.05). In comparison to controls, the mean concentration of total cholesterol was significantly lower in all the other groups and the lowest mean concentration of triglycerides was recorded in group 4 with significant difference when compared to the controls (0.9±0.4 vs 3.6±0.4 mmol/L, p<0.05). CONCLUSION: The change from HCD to a normal diet coupled with TH supplementation has been shown to reduce bodyweight, liver weight, total cholesterol and triglyceride levels in the 12% HCD NASH induced animal model

The effects of Tualang honey on sperm profile In mixed cholesterol diet administered rats

Introduction: Hypercholesterolaemia is a recognised factor associated with male infertility. They have been shown to reduce the semen quality. The main recommendation for treatment is diet modifications. Tualang honey (TH) has proven to exert anti-inflammatory and anti-oxidative effects which may help to improve sperm parameters. Methods: Thirty male Sprague Dawley rats were divided into two groups, mixed cholesterol diet (12%CD;n=24) and standard diet (SD;n=6) and were fed for 16 weeks. Then, the rats in the 12%CD group were divided into four groups and continued with SD. Group A was untreated while group B, C and D were given TH at different doses (1.2, 2.4, and 3.0g/kg/day) for 4 weeks. Then, sperm profile analysis from the caudal epididymis was performed. Results: Group A showed significant decrease in sperm concentration, the percentage of total sperm motility, progressive motility, and viability compared to SD group (p<0.001). In contrast, all TH supplemented groups demonstrated significant improvement in the sperm parameters (p<0.001). The higher the dosage of TH given, the higher the improvements in sperm parameters (p<0.001). Conclusion: TH supplementation with diet modifications improved sperm profile parameters. From our findings, there is a need to further explore TH in improving male infertility associated with hypercholesterolaemia

The effects of Tualang honey with or without diet modifications on sperm profile in high cholesterol diet induction animal model

Introduction: Hypercholesterolaemia is a recognised factor associated with male infertility. However, currently, there is limited therapy available. Tualang honey (TH) is a type of Malaysian polyfloral wild honey produced by the rock bee (Apis dorsata) that has been proven to exert both anti-inflammatory and anti-oxidative effects. This study aimed to determine the effects of TH with or without diet modifications on the sperm profile high cholesterol diet (HCD) administered rats. Methods: Thirty Sprague Dawley rats weighing 200 - 250 gm were randomly divided into the standard diet (control) group (n=6), mixed cholesterol diet (MCD) group and high cholesterol diet (HCD) group (n=12 each). The six rats in the control group were fed with standard commercial rat pellet while the 12 rats in the MCD and HCD group were fed with a 12% cholesterol diet for 16 weeks. At the end of the 16 weeks, the rats in the MCD group were divided into two subgroups (M1 and M2) and continued on standard diet in addition to administration of distilled water and 1.2 g of honey per kg body weight daily respectively for 4 weeks. The rats in the HCD group were divided into two subgroups (H1 and H2) and continued on the 12% high cholesterol diet in addition to administration of distilled water and 1.2 g of honey per kg body weight daily respectively for 4 weeks. The rats in the control group were continued with commercial rat pellets without honey supplementation. At the end of the 4 weeks, all rats were sacrificed and the cauda epididymis was collected for sperm analysis. Results: The sperm parameters (sperm concentration, the percentage of total sperm motility, progressive motility, normal sperm morphology, and viability) of rats in group M1 and H1 were significantly reduced compared to the control. In contrast, all TH supplemented groups demonstrated significant improvement in the sperm parameters. However, there were significant increase in the sperm concentration and normal sperm morphology in group M2 compared to H2. Conclusion: In conclusion, the TH supplementation with diet modifications improved the sperm analysis results in the animal model