Protective Mechanism Pathway of Swietenia macrophylla Extract Nanoparticles against Cardiac Cell Damage in Diabetic Rats.

Hyperglycemia causes cardiac cell damage through increasing ROS production during diabetic complications. The current study proves the antioxidant activity of Swietenia macrophylla (S. macrophylla) extract nanoparticles as a protector against streptozotocin (STZ)-induced cardiac cell damage. In this research, high-energy ball milling is used to create S. macrophylla extract nanoparticles. The active chemical compounds in the S. macrophylla extract nanoparticles were analyzed through phytochemical screening and GC-MS. Furthermore, we characterized the size of S. macrophylla extract nanoparticles with Dynamic Light Scattering (DLS). Forty male rats were divided randomly into five groups. In the control group, rats received aqua dest orally; in the diabetic group, rats were injected intraperitoneally with STZ; in the S. macrophylla group, rats were injected with STZ and orally given S. macrophylla extract nanoparticles. The results of phytochemical screening showed that S. macrophylla extract nanoparticles contain saponins, flavonoids, alkaloids, phenolics and tannins. Seven chemical compounds in S. macrophylla extract nanoparticles were identified using GC-MS, including phenol, piperidine, imidazole, hexadecene, heptadecanol, dihexylsulfide and heptanol. DLS showed that the S. macrophylla extract nanoparticles' size was 91.50 ± 23.06 nm. Injection with STZ significantly increased malondialdehyde (MDA) levels in cardiac tissue and creatine kinase-myocardial band (CK-MB) and lactate dehydrogenase (LDH) levels in serum. STZ also significantly reduced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and the level of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in cardiac tissue compared with the control group (p < 0.05). In contrast, the administration of S. macrophylla extract nanoparticles can prevent STZ-induced cardiac cell damage through decreasing the level of CK-MB and LDH in serum and the level of MDA in cardiac tissue. S. macrophylla extract nanoparticles also significantly increased Nrf2 expression as well as SOD and GPx levels in cardiac tissue. These effects are related to the prevention of cardiac histopathological alteration (degeneration and necrosis) in diabetic rats. These results suggest that S. macrophylla nanoparticles contain active compounds such as flavonoids, phenols, piperidine, imidazole and hexadecene and have strong antioxidant activity. These can act as a potential cardioprotective agent against STZ-induced cardiac cell damage due to its antioxidant properties.

Molecular Mechanism of Fucoidan Nanoparticles as Protector on Endothelial Cell Dysfunction in Diabetic Rats' Aortas.

Antioxidants have an important role in protecting against diabetes complications such as vascular endothelial cell damage. Fucoidan has strong antioxidant properties, therefore the aim of this study was to investigate the protective mechanism of fucoidan nanoparticles through the pathway of antioxidant activity against streptozotocin-induced diabetic aortic endothelial cell dysfunction in rats. Fucoidan nanoparticles are made utilizing high-energy ball milling. This research consists of five groups, namely: control rats, rats were administered aquadest; diabetic rats, rats were administered streptozotocin (STZ); fucoidan nanoparticle rats, rats were administered STZ and fucoidan nanoparticles. Aortic tissue was collected for the evaluation of ROS (reactive oxygen species), Malondialdehyde (MDA), superoxide Dismutase (SOD), Glutathione Peroxidase (GPx), Nuclear factor erythroid-2-related factor 2 (Nrf2), Nitric Oxide (NO), cyclic Guanosine Monophosphate (cGMP), relaxation response of acetylcholine (Ach), and the diameter of the aorta. The size distribution of the fucoidan nanoparticles was 267.2 ± 42.8 nm. Administration of fucoidan nanoparticles decreased the levels of ROS and MDA, and increased the levels of SOD, levels of GPx, Nrf2 expression, NO levels, cGMP expression, the relaxation response of Ach, and lumen diameter of the aorta, which are significantly different when compared with diabetic rats, p < 0.05. In this study, we concluded that the mechanism pathway of fucoidan nanoparticles prevents aortic endothelial cell dysfunction in diabetic rats through antioxidant activity by reducing ROS and MDA and incrementing SOD levels, GPx levels, and Nrf2 expression. All of these can lead to an elevated relaxation response effect of Ach and an increase in the lumen diameter of the aorta, which indicates a protective effect of fucoidan nanoparticles on aortic endothelial cells.

Protecting mechanism of Swietenia macrophylla ethanol extract nanoparticle on streptozotocin induced renal damage in rat.

Background: Hyperglycemia increases reactive oxygen species (ROS), which contributes to diabetic complications such as kidney cell damage. Antioxidant administration could inhibit ROS and kidney cell damage commonly seen in hyperglycemia. Aim: We want to demonstrate that the antioxidant properties of Swietenia macrophylla ethanol extract nanoparticles can prevent kidney cell damage brought on by streptozotocin (STZ) in the current investigation. Methods: This study employs high-energy ball milling to produce nanoparticles from S. macrophylla extract. Additionally, dynamic light scattering (DLS) is utilized to characterize the nanoparticle sizes of the S. macrophylla ethanol extract. Five groups, each consisting of 8 rats, were formed from 40 rats. Control rats received distilled water, the diabetic rats were administered STZ injections, while S. macrophylla rats were given S. macrophylla extract nanoparticles orally and STZ injection. After the trial, blood from a rat was drawn intracardially to check the levels of blood urea nitrogen (BUN) and creatinine. The levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) were then assessed in kidney tissue samples. Histological alterations were evaluated in kidney section samples. Results: A DLS analysis estimated the size of the S. macrophylla ethanol extract nanoparticles to be about 91.50 ± 23.06 nm. BUN and creatinine levels were significantly raised after STZ treatment. STZ significantly decreased SOD and GPx levels in kidney tissue while raising MDA levels (p < 0.05). Swietenia macrophylla ethanol extract nanoparticle caused the decreased levels of BUN and creatinine in blood to normal levels (p < 0.05), indicating that S. macrophylla ethanol extract prevented the STZ-induced kidney cell damage. Additionally, S. macrophylla nanoparticles significantly raise GPx and SOD levels in kidney tissue while lowering MDA levels (p < 0.05). These actions are thought to have prevented kidney histological alterations (degeneration and necrosis) in diabetic rats. Conclusion: According to these results, the anti-oxidative stress properties of S. macrophylla nanoparticles make them potentially effective nephroprotective therapies for STZ-induced kidney cell damage.

Antioxidative Stress and Anti-Inflammatory Activity of Fucoidan Nanoparticles against Nephropathy of Streptozotocin-Induced Diabetes in Rats.

Oxidative stress and inflammation have been shown to interact and have the role of importance in causing diabetic nephropathy complications. Fucoidan has a strong antioxidant and anti-inflammation effect, so the aim of this research was to evaluate the antioxidative stress and anti-inflammatory effect of fucoidan nanoparticles against nephropathy of streptozotocin-induced diabetes in rats. Fucoidan nanoparticles are characterized using dynamic light scattering (DLS) and scanning electron microscope (SEM). The rats were randomized into the control group (were given with aquadest), streptozotocin group (were injected with streptozotocin at a dose of 55 mg/kg BW i.p.), and fucoidan nanoparticle group (were given orally with fucoidan at doses 75, 150, and 300 mg/kg BW and then injected streptozotocin at a dose of 55 mg/kg BW i.p.). The blood was taken to evaluate the level of blood urea nitrogen (BUN) and creatinine. The kidney tissues were collected to measure malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) by ELISA; superoxide dismutase (SOD), and glutathione peroxidase (GPx) by immunohistochemical staining and histological observation by Hematoxylin & Eosin (H&E) staining. The DLS demonstrated that the fucoidan nanoparticle size was 330.6 ± 58.8 nm, and the SEM showed an irregular shape with a rough surface image. The administration of streptozotocin significantly increased BUN, creatinine, MDA, IL-6, and TNF-α levels, whereas expression of SOD and GPx decreased as compared with the control group (p < 0.05). The administration of fucoidan nanoparticles only at a dose of 300 mg/kg BW significantly decreases BUN, creatinine, MDA, IL-6, and TNF-α levels. However, fucoidan nanoparticles at a dose of 300 mg/kg BW significantly increase SOD and GPx expression as compared with the streptozotocin group (p < 0.05). The administration of streptozotocin caused the loss of normal kidney cell structure and necrosis, while treatment with fucoidan nanoparticles improved renal cell necrosis. It can be concluded that fucoidan nanoparticles are promising agents in terms of the protection afforded against streptozotocin-induced nephropathy through antioxidative stress by decreasing MDA and increasing SOD and GPx and through anti-inflammatory effect by decreasing levels of IL-6 and TNF-α.

Antioxidative Stress and Antiapoptosis Effect of Chitosan Nanoparticles to Protect Cardiac Cell Damage on Streptozotocin-Induced Diabetic Rat.

The antioxidant can inhibit oxidative stress and apoptosis, which has a role in an important mechanism on diabetic-induced cardiac cell damage. The research goal was to prove the antioxidative stress and antiapoptosis effect of chitosan nanoparticles as a cardioprotector in streptozotocin-induced diabetic rats. Scanning electron microscope (SEM) and dynamic light scattering (DLS) characterize the chitosan nanoparticles. This research is a laboratory experiment which consists of the control group (rats were given distilled water), the streptozotocin group (rats were injected streptozotocin at dose of 55 mg/kg BW i.p), and the chitosan nanoparticle group (rats were given streptozotocin at dose 55 mg/kg BW i.p, and then given chitosan nanoparticles at dose 75 mg/kg BW, 150 mg/kg BW, and 300 mg/kg BW peroral). Creatine kinase-myoglobin (CK-MB) and lactate dehydrogenase (LDH) were measured from the blood sample. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) from cardiac tissue were examined by ELISA; nuclear factor erythroid 2-related factor 2 (Nrf2) was evaluated by western blotting; B-cell lymphoma 2 (Bcl-2) and Caspase-3 expression were investigated by immunohistochemical staining and also were evaluated histological preparation by hematoxylin & eosin (H&E) staining. The chitosan nanoparticles have a rough surface and an irregular shape. Its size is 247.3 ± 38.1 µm. Streptozotocin injection significantly increased the levels of CK-MB, LDH, MDA, and expression of caspase-3. In contrast, the levels of SOD, GPx, Nrf2, and expression of Bcl-2 decreased as compared with the control group (p < 0.05). This is accompanied by the loss of normal cardiac cell structure and necrosis. The administration of chitosan nanoparticles significantly reduced levels of CK-MB, LDH, MDA, and expression of Caspase-3. However, the levels of SOD, GPx, Nrf2, and expression of Bcl-2 increased as compared with the streptozotocin group (p < 0.05). And also, chitosan nanoparticles inhibited cell necrosis in diabetic rats. This study suggests that the administration of chitosan nanoparticles can protect cardiac cell damage in diabetic rats through antioxidative stress by decreasing ROS and increasing Nrf2 expression, level of SOD, and GPx and through antiapoptosis by increasing expression of Bcl-2 and decreasing expression of Caspase-3.

The Potency of Red Seaweed (Eucheuma cottonii) Extracts as Hepatoprotector on Lead Acetate-induced Hepatotoxicity in Mice.

BACKGROUND: Lead is one of the most toxic metals, producing severe organ damage in animals and humans. Oxidative stress is reported to play an important role in lead acetate-induced liver injury. AIM: This study was carried out to investigate the role of ethanol extract of Eucheuma cottonii in protecting against lead acetate-induced hepatotoxicity in male mice. MATERIALS AND METHODS: The sample used fifty male mice which were divided into five groups: negative control (mice were given daily with Aquadest); positive control (mice were given daily with lead acetate 20 mg/kg body weight (BW) orally once in a day for 21 days); and the treatment group (mice were given E. cottonii extracts 200 mg, 400 mg, and 800 mg/kg BW orally once in a day for 25 days, and on the 4th day, were given lead acetate 20 mg/kg BW 1 h after E. cottonii extract administration for 21 days). On day 25, the levels of serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), alkaline phosphatase (ALP), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were measured. The data of SGOT, SGPT, ALP, MDA, SOD, and GPx were analyzed with one-way ANOVA, followed by least significant difference test. RESULTS: The results showed that oral administration of lead acetate 20 mg/kg BW for 21 days resulted in a significant increase in SGOT, SGPT, ALP, and MDA levels. Moreover, there was a significant decrease in SOD and GPx levels. Treatment with E. cottonii extracts of 800 mg/kg BW but not with 200 mg/kg BW and 400 mg/kg BW significantly (P < 0.05) decreased the elevated SGPT, SGOT, ALP, and MDA levels as compared to positive control group. Treatment with E. cottonii extracts of 800 mg/kg BW also showed a significant increase in SOD and GPx levels as compared to positive control group. Treating mice with lead acetate showed different histopathological changes such as loss of the normal structure of hepatic cells, blood congestion, and fatty degeneration whereas animals treated with lead acetate and E. cottonii extracts showed an improvement in these changes and the tissue appeared with normal structures. CONCLUSION: It can be concluded that E. cottonii extracts could be a potent natural product and can provide a promising hepatoprotective effect against lead acetate-induced hepatotoxicity in mice. SUMMARY: In summary, Oxidative stress reported to play an important role in lead acetate induced liver injury. The lead acetate treatment significantly increased the SGOT, SGPT, ALP, MDA, and decreased the antioxidant enzymes (SOD and GPx) in liver. The inhibition of antioxidant enzymes will increase free radicals in liver tissues and might induce liver injury in mice. The presence of ethanol extract of Eucheuma cottonii with lead acetate showed protective effects as attenuating lead acetate against its liver toxicity, and this may be due to the activity of ethanol extract of Eucheuma cottonii as antioxidant. The antioxidant enzymes (SOD and GPx) were increased, and MDA, SGOT, SGPT, ALP were decreased after ethanol extract of Eucheuma cottonii administration. The enzymatic activities (SOD and GPx) and MDA in mice can be used as biomarkers of heavy metal toxicity such as lead acetate. Histopathological view of liver sections in the lead acetate treated group showed the liver damage, as compared to the negative control group. However, administration of ethanol extract of Eucheuma cottonii significantly improved the histopathological in liver of lead acetate-treated mice. From the results of this study we concluded that the ethanol extract of Eucheuma cottonii could be a potent natural product provide a promising protective effect against lead acetate induced liver toxicity in mice. Abbreviations Used: SGOT: Serum Glutamic Oxaloacetic Transaminase, SGPT: Serum Glutamic Pyruvate Transaminase, ALP: Alkaline Phosphatase, MDA: Malondialdehyde, SOD: Superoxide Dismutase, GPx: Glutathione Peroxidase.