Molecular mechanisms of resveratrol and its silver nanoparticle conjugate in addressing sepsis-induced lung injury.

Sepsis is a life-threatening condition characterized by a systemic inflammatory response to infection. Despite extensive research on its pathophysiology, effective therapeutic approaches remain a challenge. This study investigated the potential of resveratrol (RV) and silver nanoparticle-enhanced resveratrol (AgNP-RV) as treatments for sepsis-induced lung injury using a rat model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). The study focused on evaluating changes in oxidative status (TAS, TOS, and OSI) and the expression of inflammatory and apoptotic markers (IL-1ß, TNF-α, P2X7R, TLR4, Caspase-3, and Bcl-2) in lung tissue. Both RV and AgNP-RV demonstrated potential in mitigating oxidative stress, inflammation, and apoptosis, with AgNP-RV exhibiting greater efficacy than RV alone (p < 0.05). These findings were corroborated by histopathological analyses, which revealed reduced tissue damage in the RV- and AgNP-RV-treated groups. Our study highlights the therapeutic potential of RV and, particularly, AgNP-RV in combating sepsis-induced oxidative stress, inflammation, and apoptosis. It also underscores the promise of nanoparticle technology in enhancing therapeutic outcomes. However, further investigations are warranted to fully understand the mechanisms of action, especially concerning the role of the P2X7 receptor in the observed effects. Nonetheless, our research suggests that RV and AgNP-RV hold promise as novel strategies for sepsis management.

Astaxanthin treatment reduces kidney damage and facilitates antioxidant recovery in lithium-intoxicated rats.

OBJECTIVE: This study aimed to evaluate the protective effects of astaxanthin against lithium-induced nephrotoxicity, focusing on histopathological changes, oxidative stress modulation, and alteration in the expression of key proteins related to apoptosis and inflammation. METHODS: In this study, 56 male rats were utilized and divided into experimental groups subjected to lithium-induced nephrotoxicity, with and without astaxanthin treatment, over 14 and 28 days. The parameters assessed included oxidative stress markers (MDA, GSH, SOD), protein expression levels of BCL-2, BAX, TNF- α, PI3K, NF-κ B-p65, IL-1ß, and comprehensive histopathological examinations to evaluate the integrity of renal tissue. RESULTS: Lithium exposure led to significant renal damage, as evidenced by histological distortions in renal architecture, increased oxidative stress indicated by elevated MDA levels, and dysregulated expressions of apoptotic and inflammatory proteins. Notably, histopathological analysis revealed glomerular and tubular degeneration in lithium-treated groups. Astaxanthin treatment effectively mitigated these effects, demonstrating its efficacy in reducing lipid peroxidation, rebalancing apoptotic proteins, suppressing pro-inflammatory cytokines, and preserving renal histological structure. The concurrent use of lithium and astaxanthin showed a considerable amelioration of lithium-induced damage, suggesting astaxanthin's role in attenuating the nephrotoxic effects of lithium, both at a molecular and structural level. CONCLUSION: Astaxanthin demonstrates significant renoprotective effects against lithium-induced nephrotoxicity, suggesting its utility as an effective adjunctive therapy. Through its potent antioxidative, anti-inflammatory, and anti-apoptotic actions, astaxanthin effectively reduces renal damage associated with lithium treatment, underscoring its potential for enhancing renal health in patients receiving lithium therapy.

Anticarcinogenic Effects of Gold Nanoparticles and Metformin Against MCF-7 and A549 Cells.

Metformin is commonly prescribed to people with diabetes. Metformin has been shown in previous studies to be able to prevent the growth of cancer cells. This study aims to investigate the effects of metformin and gold nanoparticles in MCF7 breast cancer and A549 lung cell lines. The effects of metformin and gold nanoparticles on MCF7 breast cancer and A549 lung cells were determined on cells grown in 24 h cell culture. MCF-7 and A549 cells were incubated for 24 h with the treatment of escalating molar concentrations of ifosfamide. The MTT assay was used to determine the cytotoxicity of metformin toward MCF7 and A549 cell lines. The expression of Bax, BCL2, PI3K, Akt3, mTOR, Hsp60, Hsp70, and TNF-α was measured by RT-PCR. Metformin and gold nanoparticles inhibited the proliferation of MCF-7 and A549 cells in a dose and time-dependent manner with an IC50 value of 5 µM and 10 µg/mL. RT-PCR assays showed ifosfamide + metformin + gold nanoparticles significantly reduced the expression of BCL2, PI3K, Akt3, mTOR, Hsp60 and Hsp70 and increased the expression of TNF-α and Bax. The findings obtained in this study suggest that further studies should be conducted, and metformin and gold nanoparticles can be used in breast cancer and lung cancer treatments.

Silver Nanoparticles Loaded with Oleuropein Reduce Doxorubicin-Induced Testicular Damage by Regulating Endoplasmic Reticulum Stress, and Apoptosis.

Doxorubicin (DOX) is the most used chemotherapeutic agent for treating solid tumors. DOX treatment may lead to testicular damage using oxidative stress, resulting in infertility. These adverse effects may be prevented by the activation of antioxidant systems. Oleuropein (OLE) is a powerful flavonoid with several ameliorative effects, including antioxidative, antiproliferative, and anti-inflammatory. It would be more efficient and applicable in treating chronic human diseases if its poor bioavailability improves with a nano-delivery system. The current study aims to assess the histopathological changes and antioxidative effects of OLE loaded with silver nanoparticles oleuropein (OLE-AgNP) on the testicular injury triggered by DOX in rats. Forty-eight male albino rats were randomly divided into six groups as follows: the control, DOX (2.5 mg/kg), OLE (50 mg/kg), AgNP (100 mg/kg), OLE + AgNP (50 mg/kg), OLE (50 mg/kg) + DOX (2.5 mg/kg), AgNP (100 mg/kg) + DOX (2.5 mg/kg), and OLE-AgNP (50 mg/kg) + DOX (2.5 mg/kg) for 11 days. Oxidative stress, inflammation, apoptosis, endoplasmic reticulum stress markers, sperm analysis, and histopathological analyses were performed on testicular tissues taken from rats decapitated after the applications and compared between the experimental groups. The tissue MDA level was lower in the OLE and OLE+AgNP-treated groups than in the DOX-treated group. In addition, SOD and GSH levels significantly increased in both the OLE and OLE+AgNP-treated groups compared to the DOX group. Both OLE and OLE+AgNP, particularly OLE+AgNP, ameliorated DOX-induced testicular tissue injury, as evidenced by reduced injury and improved seminiferous tubules and spermatocyte area. In addition, OLE and OLE+AgNP, especially OLE+AgNP, inhibited DOX-induced testicular tissue inflammation, apoptosis, and endoplasmic reticulum stress. The findings suggest that nanotechnology and the production of OLE+AgNP can ameliorate DOX-induced testicular damage.

Assessment of toxicological effects of favipiravir (T-705) on the lung tissue of rats: An experimental study.

This study aimed to present new data on the side effects of favipiravir on healthy lung tissue and the respiratory system. In the study, two different durations (5 and 10 days) were preferred to determine the effect of favipiravir treatment due to clinical improvement rates of approximately 5 and 10 days during the use of favipiravir in COVID-19 patients. In addition, after 10 days of favipiravir treatment, animals were kept for 5 days without any treatment to determine the regeneration of lung tissues. Favipiravir was administered to rats by oral gavage at a daily dose of 200 mg/kg for 5 and 10 days, as in previous studies. At the end of the experiment, the histopathological and biochemical effects of favipiravir in the lung tissue were investigated. The data obtained from the study showed that favipiravir increased oxidative stress parameters, expression of apoptotic markers, and pro-inflammatory markers in lung tissue. Since malondialdehydes is an oxidant parameter, it increased in favipiravir-administered groups; It was determined that the antioxidant parameters glutathione, superoxide dismutase, glutathione peroxidase, and catalase decreased. Other markers used in the analysis are Bcl-2, Bax, NF-κB, interleukin (IL)-6, Muc1, iNOS, P2X7R, IL-6 and caspase-3. The levels of Bax, caspase-3, NF-κB, IL-6, Muc1, and P2X7R were increased in the Fav-treated groups compared with the control. However, the levels of Bcl-2 decreased in the Fav-treated groups. The present study proves that favipiravir, widely used today, causes side effects in lung tissue.

Radioprotective role of amifostine on osteointegration of titanium implants in the tibia of rats.

BACKGROUND: Titanium is the most widely used metal for bone integration, especially for cancer patients receiving ionizing radiation. This study aimed to investigate the amifostine administration that would reduce the effects of radiation on bone healing and osseointegration in rat models. OBJECTIVES: It is aimed that the application of amifostine in rats receiving radiotherapy treatment will reduce the negative effects of ionizing radiation on the bone. METHODS: Thirty-five adult male Wistar rats were randomly divided into one healthy and four experimental groups. In three consecutive days, two experimental groups of rats (AMF-RT-IMP and RT-IMP) were exposed to radiation (15 Gy/3 fractions of 5 Gy each). Then the titanium implants were inserted into the left tibia. Before the radiotherapy process, a 200 mg/kg dose of amifostine (AMF) was administered to the rats in the AMF-IMP and AMF-RT-IMP groups. Twenty-eight days after the screw implant, all rats were sacrificed, and their blood samples and tibia bones were collected for analysis. RESULTS: The results indicated an accelerated bone formation and a more rapid healing process in the screw implants in the AMF-IMP, AMF-RT-IMP, and AMF-RT groups than in the RT-IMP group. Also, bone-implant contact area measurement and inflammation decreased with amifostine treatment in the implants subjected to irradiation (p < 0.05). CONCLUSIONS: The results obtained in the present study suggested that amifostine prevents the losses of bone minerals, bone integrity, and implant position from ionizing-radiation when given before exposure.

Investigation of the endometrial receptivity status in experimental hypothyroid-induced female rats.

Objectives: This study aimed to investigate hypothyroidism's effects on endometrial receptivity, creating an experimental hypothyroidism model in female rats. Materials and Methods: To induce hypothyroidism in rats of Hipotiroid-ER and Treatment-ER groups, 0.05% 6-propyl-2-thiouracil was freshly added to their drinking water for 8 weeks and then the endometrial receptivity model was applied and sacrificed on the fifth day. In the Treatment-ER group, after sc-administration of 0.8 µg/100 g L-thyroxine for 10 days, the endometrial receptivity model was applied to the rats and sacrificed on the fifth day. Results: In the histopathological evaluation, epithelial degeneration, vacuolization, enlargement of the uterine glands, and morphological disorders were observed in the endometrial layer of the Hypothyroid-ER group. However, these pathologies were significantly alleviated in the Treatment-ER group. Integrin ß3, integrin αvß3, LIF, and HOXA10 immune reaction intensities were high in the Control-ER and Treatment-ER groups, while in the Hypothyroid-ER group, integrin ß3, integrin αvß3, LIF, and HOXA10 immunoreactivity intensities were low. Also, while MUC1 immunoreactivity was high in the Hypothyroid-ER group, it was low in the other groups. In biochemical analysis, a significant increase in the TSH and progesterone levels and a significant decrease in the FT4, E2, FSH, and LH levels in the Hypothyroid-ER group compared with the Control-ER group were observed. Also, all hormone levels were significantly ameliorated in the rats of the Treatment-ER group compared with the Hypothyroid-ER group. Conclusion: The results obtained showed that hypothyroidism had a significant effect on endometrial receptivity-the histopathological and biochemical changes caused by hypothyroidism in the experimental rat model were ameliorated with L-thyroxine treatment.

Potential protective effect of astaxanthin on ovary ischemia-reperfusion injury.

Objectives: We thought that astaxanthin (ASX) might be a protective agent in oxidative stress damage that develops against ischemia and reperfusion injury in the rat ovary. Materials and Methods: The experimental groups consisted of healthy, I (Ischemia), I+ASX50, I+ASX100, I/R (Ischemia/Reperfusion), I/R+ ASX50, and I/R+ ASX100. Vascular clamps were applied to the ovaries for 3 hr to induce ischemia. For the reperfusion groups, the clamps were opened and blood flow was restored to the ovaries for 3 hr. At the end of the experiment, biochemical, histopathological, and immunohistochemical analyses were made from the tissue samples taken. Results: While MDA levels increased significantly in I and I/R groups, SOD levels decreased. It was found that ASX significantly decreased MDA levels and increased SOD activity in treatment groups depending on the dose. Caspase 3, IL-1 ß, and IL-6 expressions were severely increased in ischemia and I/R groups, while the severity of I+ASX50 and I/R+ASX100 immunoreactivity was decreased. While severe hemorrhage areas were observed in I and IR groups, minimal hemorrhage areas were observed in the treatment groups, especially in I/R+ASX100 groups. In addition, inflammatory cells and necrotic cells in the I/R group were not observed in I/R+ASX50 and I/R+ASX100 groups. Conclusion: As a result, it was determined that ASX has a strong protective role against oxidative damage in the treatment of ovarian ischemia-reperfusion injury.

The effects of dragon fruit (Hylocereus polyrhizus) extract on indomethacin-induced stomach ulcer in rats.

The aim of this study was to investigate the effects of red dragon fruit (Hylocereus polyrhizus) extract (DFE) on the stomach in ulcer model induced by indomethacin in rats. Effects of DFE were evaluated in indomethacin-induced gastric damage model on Sprague-Dawley rats. Experimental model: all rats were fasted for 24 h. At the end of this period, DFE was administered to the ulcer-induced groups. One hour after this application, a dose of 25 mg/kg of indomethacin was applied by oral gavage to all groups except the HEALTHY and DFE1000 groups. Six hours after indomethacin administration, the rats were euthanized with high-dose anesthesia and the experiment was terminated. Macroscopic and microscopic analyses for investigating ulcerative area, molecular and biochemical analyses for oxidative damages investigation and molecular analyses for the effect mechanism of indomethacin and DFE were conducted on stomach tissues in the study. While oxidative stress-associated markers such as MDA, BAX, and Caspase 3 increased dramatically in the indomethacin group, GSH antioxidant levels decreased. It was observed that these parameters were significantly improved in DFE 500 mg/kg and DFE 1000 mg/kg groups compared to ulcer group, and the results of especially DFE 1000 mg/kg group were similar to famotidine group. We observed that our histopathological findings also supported all our other findings. Dragon fruit extract was protected against indomethacin-induced ulcer damage by decreased MDA levels, increased GSH levels, and inhibition of Caspase 3, BAX, and Cox-2, and activation of Cox-1. PRACTICAL APPLICATIONS: People of all ages around the world suffer from gastric ulcer which is one of the most common gastrointestinal ailments. The etiological factors of the disease are using of cigarette and alcohol, nutritional deficiencies, infections, and using non-steroidal anti-inflammatory drugs which use frequent and indiscriminate. Indomethacin is one of the NSAIDs and is commonly preferred to induce ulcer modeling in rats due to its gastric toxicity potential. Current anti-ulcer drugs have many serious side effects. Patients who suffered from gastric ulcer tend to discontinue the drug because of side effects. Therefore, patients need new agents that are non-toxic, have few side effects, and are easily accessible anti-ulcer drugs. Dragon fruit, as a medicinal herb, is highly valuable and widely used in traditional medicine, and may provide gastroprotective activity. Studies have shown that H. polyrhizus has antioxidant activities. We consider the effects of dragon fruit extract (DFE) to be a therapeutic drug for an indomethacin-induced ulcer model.

The Effects of Hesperidin and Quercetin on Serum Tumor Necrosis Factor-Alpha and Interleukin-6 Levels in Streptozotocin-induced Diabetes Model.

BACKGROUND: Diabetes mellitus (DM) is a metabolic disorder that occurs as a result of absolute or relative insufficiency of insulin release and/or insulin effect due to impairment of carbohydrate, fat and protein metabolism, and it is characterized by hyperglycemia and leads to various complications. OBJECTIVE: In this study, it was aimed to investigate the effects of hesperidin (HP) and quercetin, which are natural flavonoids, on serum malondialdehyde (MDA), glutathione (GSH), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) levels in rats with streptozotocin (STZ)-induced diabetes. MATERIALS AND METHODS: The experimental animals were divided into four groups, each group comprising ten rats designated as follows: Group 1 served as control rats (C); Group 2 served as diabetic rats (DM); Group 3 served as diabetic rats administered HP (DM + HP) (100 mg/kg b. w.); and Group 4 served as diabetic rats administered quercetin (DM + Q) (100 mg/kg b. w.). RESULTS: Serum MDA and GSH levels were significantly higher in STZ-induced DM group than control group (P < 0.05). In DM + HP and DM + Q groups, MDA levels were significantly decreased compared to DM groups (P < 0.05), but there was no significant difference GSH levels between DM, DM + HP, and DM + Q groups (P > 0.05). TNF-α levels in STZ-induced DM group were significantly decreased compared to control group (P < 0.05), and groups of DM + HP and DM + Q had higher serum TNF-α levels than STZ-induced DM group (P < 0.05). In STZ-induced DM group, serum IL-6 levels were decreased compared to control group (P < 0.05). CONCLUSION: As a result, in this study, we determined that HP and quercetin may play an effective role in regulating insulin metabolism metabolism in diabetes. However, considering the incompatibility of various results in the literature as well as our own results, we think that the actual role of cytokines in the pathogenesis of diabetes is one of the issues that need to be clarified in further studies. SUMMARY: Hesperidin (HP) and quercetin reduced the insulin, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and malondialdehyde (MDA) serum levels and raised the glutathione (GSH) levels compared to diabetes mellitus (DM) groupSZT-induced DM increased the MDA serum levels and decreased the GSH levels compared to control groupHP and quercetin-treated rats showed higher interleukin-6 and tumor necrosis factor alpha cytokine levels than DM groupHP and quercetin may play an effective role in regulating insulin metabolism in diabetes. Abbreviations used: DM: Diabetes mellitus, MDA: Malondialdehyde, GSH: Glutathione; IL-6: Interleukin-6, TNF-α: Tumor necrosis factor alpha, HP: Hesperidin, Q; Quercetin, STZ: Streptozotocin, TC: Total cholesterol, TG: Triglyceride, HDL-C: High density lipoprotein cholesterol, LDL-C: Low density lipoprotein cholesterol, VLDL-C: Very-low-density lipoprotein cholesterol.