Melatonin Mitigates Cisplatin-Induced Submandibular Gland Damage by Inhibiting Oxidative Stress, Inflammation, Apoptosis, and Fibrosis.

BACKGROUND: The study aims to examine the possible effect of melatonin against cisplatin-induced submandibular degeneration in experimental rats exploring its ameliorative mechanisms. METHODS: Rats were classified into four experimental groups; control group; melatonin group; cisplatin group; and cisplatin+melatonin group. Submandibular tissues were collected. Biochemical, histopathological, and immunohistopathological examination and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis were performed. RESULTS: The results indicate that intraperitoneal administration of melatonin (30 mg/kg body weight) alongside cisplatin significantly elevated submandibular glands (SMG) and reduced glutathione (GSH) and superoxide dismutase (SOD) levels (p < 0.001), while it reduced malondialdehyde (MDA) levels, NF-κB gene expression, the protein level of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1ß), immunoexpression of low-dose cyclooxygenase-2 (Cox-2), and CD68. Moreover, melatonin reduced immune and gene expression of alpha-smooth muscle actin (α-SMA), immunoexpression of caspase-3, and gene expression of Bax in comparison to the cisplatin group. CONCLUSION: Melatonin attenuated cisplatin-induced submandibular destruction alleviating SMG oxidative stress, inflammation, and fibrosis in addition to halting cellular apoptosis, sheds light on its usage in clinical application.

Coenzyme Q10 mitigates cadmium cardiotoxicity by downregulating NF-κB/NLRP3 inflammasome axis and attenuating oxidative stress in mice.

Coenzyme Q10 (CoQ10) occurs naturally in the body and possesses antioxidant and cardioprotective effects. Cardiotoxicity has emerged as a serious effect of the exposure to cadmium (Cd). This study investigated the curative potential of CoQ10 on Cd cardiotoxicity in mice, emphasizing the involvement of oxidative stress (OS) and NF-κB/NLRP3 inflammasome axis. Mice received a single intraperitoneal dose of CdCl2 (6.5 mg/kg) and a week after, CoQ10 (100 mg/kg) was supplemented daily for 14 days. Mice that received Cd exhibited cardiac injury manifested by the elevated circulating cardiac troponin T (cTnT), CK-MB, LDH and AST. The histopathological and ultrastructural investigations supported the biochemical findings of cardiotoxicity in Cd-exposed mice. Cd administration increased cardiac MDA, NO and 8-oxodG while suppressed GSH and antioxidant enzymes. CoQ10 decreased serum CK-MB, LDH, AST and cTnT, ameliorated histopathological and ultrastructural changes in the heart of mice, decreased cardiac MDA, NO, and 8-OHdG and improved antioxidants. CoQ10 downregulated NF-κB p65, NLRP3 inflammasome, IL-1ß, MCP-1, JNK1, and TGF-ß in the heart of Cd-administered mice. Moreover, in silico molecular docking revealed the binding potential between CoQ10 and NF-κB, ASC1 PYD domain, NLRP3 PYD domain, MCP-1, and JNK. In conclusion, CoQ10 ameliorated Cd cardiotoxicity by preventing OS and inflammation and modulating NF-κB/NLRP3 inflammasome axis in mice. Therefore, CoQ10 exhibits potent therapeutic benefits in safeguarding cardiac tissue from the harmful consequences of exposure to Cd.

Acceleration of Wound Healing in Diabetic Rats through a Novel 3D Organo-Hydrogel Nanocomposite of Polydopamine/TiO2 Nanoparticles and Cu (PDA-TiO2@Cu).

BACKGROUND: Diabetic wound represents a serious issue with a substantial impact and an exceptionally complex pathology affecting patients' mental health and quality of life. So, we have developed a novel 3D organo-hydrogel nanocomposite of polydopamine/TiO2 nanoparticles and cu (PDA-TiO2@Cu) and examined its efficacy in diabetic wound healing. METHODS: Forty-five adult male albino rats were divided into normal control rats (non-diabetic rats with non-treated skin wounds), diabetic control rats (diabetic rats with non-treated skin wounds), and organo-hydrogel-treated rats (diabetic wounds treated with topically applied organo- hydrogel once daily). Macroscopic changes of the wound were observed on days 0, 3, 5, 7, and 10 to measure wound diameters. Skin specimens from the wound tissue were taken on days 3, 7, and 10, respectively, and examined histologically and immunohistochemically. Also, the gene expressions of collagen I, Matrix Metalloproteinase-9 (MMP-9), and Epidermal Growth Factor (EGF), and levels of Interleukin 6 (IL-6) and Superoxide Dismutase (SOD) were assessed. RESULTS: Our observed results indicated that the developed patch significantly accelerated the healing time compared to the normal control and diabetic control groups. Moreover, the patchloaded group revealed complete re-epithelization and a highly significant increase in the mean area % of CD31 immunostaining on day 7. The organo-hydrogel-loaded group displayed a significant decrease in gene expression of MMP-9 and a significant increase in gene expression of EGF and collagen I. Additionally, the organo-hydrogel-loaded group exhibited a significant decrease in levels of IL-6 and a significant increase in levels of SOD, compared to the normal diabetic control groups. CONCLUSION: The organo-hydrogel can be used for treating and decreasing the healing period of diabetic wounds.

Amentoflavone Mitigates Cyclophosphamide-Induced Pulmonary Toxicity: Involvement of -SIRT-1/Nrf2/Keap1 Axis, JAK-2/STAT-3 Signaling, and Apoptosis.

Background and objectives: Cyclophosphamide (CPA) is an alkylating agent that is used for the management of various types of malignancies and as an immunosuppressive agent for the treatment of immunological disorders. However, its use is limited by its potential to cause a wide range of pulmonary toxicities. Amentoflavone (AMV) is a flavonoid that had proven efficacy in the treatment of disease states in which oxidative stress, inflammation, and apoptosis may play a pathophysiologic role. This study investigated the potential ameliorative effects of the different doses of AMV on CPA-induced pulmonary toxicity, with special emphasis on its antioxidant, anti-inflammatory, and apoptosis-modulating effects. Materials and methods: In a rat model of CPA-induced pulmonary toxicity, the effect of AMV at two dose levels (50 mg/kg/day and 100 mg/kg/day) was investigated. The total and differential leucocytic counts, lactate dehydrogenase activity, and levels of pro-inflammatory cytokines in the bronchoalveolar lavage fluid were estimated. Also, the levels of oxidative stress parameters, sirtuin-1, Keap1, Nrf2, JAK2, STAT3, hydroxyproline, matrix metalloproteinases 3 and 9, autophagy markers, and the cleaved caspase 3 were assessed in the pulmonary tissues. In addition, the histopathological and electron microscopic changes in the pulmonary tissues were evaluated. Results: AMV dose-dependently ameliorated the pulmonary toxicities induced by CPA via modulation of the SIRT-1/Nrf2/Keap1 axis, mitigation of the inflammatory and fibrotic events, impaction of JAK-2/STAT-3 axis, and modulation of the autophagic and apoptotic signals. Conclusions: AMV may open new horizons towards the mitigation of the pulmonary toxicities induced by CPA.

Liposome-Encapsulated Berberine Alleviates Liver Injury in Type 2 Diabetes via Promoting AMPK/mTOR-Mediated Autophagy and Reducing ER Stress: Morphometric and Immunohistochemical Scoring.

In the advanced stages of type 2 diabetes mellitus (T2DM), diabetic liver damage is a common complication that can devastate a patient's quality of life. The present study investigated the ability of liposomal berberine (Lip-BBR) to aid in ameliorating hepatic damage and steatosis, insulin homeostasis, and regulating lipid metabolism in type 2 diabetes (T2DM) and the possible pathways by which it does so. Liver tissue microarchitectures and immunohistochemical staining were applied during the study. The rats were divided into a control non-diabetic group and four diabetic groups, which are the T2DM, T2DM-Lip-BBR (10 mg/kg b.wt), T2DM-Vildagliptin (Vild) (10 mg/kg b.wt), and T2DM-BBR-Vild (10 mg/kg b.wt + Vild (5 mg/kg b.wt) groups. The findings demonstrated that Lip-BBR treatment could restore liver tissue microarchitectures, reduce steatosis and liver function, and regulate lipid metabolism. Moreover, Lip-BBR treatment promoted autophagy via the activation of LC3-II and Bclin-1 proteins and activated the AMPK/mTOR pathway in the liver tissue of T2DM rats. Lip-BBR also activated the GLP-1 expression, which stimulated insulin biosynthesis. It decreased the endoplasmic reticulum stress by limiting the CHOP, JNK expression, oxidative stress, and inflammation. Collectively, Lip-BBR ameliorated diabetic liver injury in a T2DM rat model with its promotion activity of AMPK/mTOR-mediated autophagy and limiting ER stress.

Arthrospira platensis nanoparticles defeat against diabetes-induced testicular injury in rat targeting, oxidative, apoptotic, and steroidogenesis pathways.

Varieties of studies have been used to investigate the health benefits of Spirulina (Arthrospira platensis); however, more research is needed to examine if its nano form may be utilized to treat or prevent several chronic diseases. So, we designed this study to explore the effect and the cellular intracellular mechanisms by which Arthrospira platensis Nanoparticles (NSP) alleviates the testicular injury induced by diabetes in male Wistar rats. Eighty Wistar male rats (n = 80) were randomly allocated into eight groups. Group 1 is untreated rats (control), Group 2 including STZ-induced diabetic rats with 65 mg/kg body weight STZ (STZ-diabetic), Group 3-5: including diabetic rats treated with NSP1, NSP2, and NSP3 at 0.25, 0.5, and 1 mg/kg body weight, respectively, once daily orally by the aid of gastric gavage for 12 consecutive weeks and groups 6-8 include normal rats received NSP (0.25, 0.5, and 1 mg/kg body weight once daily orally. The identical volume of normal saline was injected into both control and diabetic rats. After 12 weeks of diabetes induction, the rats were killed. According to our findings, NSP administration to diabetic rats enhances the total body weight and the weight of testes and accessory glands; in addition, NSP significantly reduced nitric oxide and malondialdehyde in testicular tissue improved sperm parameters. Intriguingly, it raises testicular GSH and SOD activity by a significant amount (p < 0.05). As well, Oral administration of NSP to diabetic rats resulted in a decrease in the blood glucose levels, HA1C, induced in the diabetic group, which overcame the diabetic complications NSP caused down-regulation of apoptotic genes with upregulation of BCL-2 mRNA expression (p < 0.05) and prominent up-regulation of steroidogenesis genes expression level in testes in comparison to the diabetic rats which resulted in improving the decreased levels of testosterone hormone, FSH, and LH induced by diabetes. In the same way, our histopathological findings support our biochemical and molecular findings; in conclusion, NSP exerted a protective effect against reproductive dysfunction induced by diabetes not only through its high antioxidant and hypoglycemic action but also through its down-regulation of Apoptotic genes and up-regulation of steroidogenesis regulatory genes expression level in diabetic testes.

Ginseng® Alleviates Malathion-Induced Hepatorenal Injury through Modulation of the Biochemical, Antioxidant, Anti-Apoptotic, and Anti-Inflammatory Markers in Male Rats.

This study aims to see if Ginseng® can reduce the hepatorenal damage caused by malathion. Four groups of forty male Wistar albino rats were alienated. Group 1 was a control group that got orally supplied corn oil (vehicle). Group 2 was intoxicated by malathion dissolved in corn oil orally at 135 mg/kg/day. Group 3 orally received both malathion + Panax Ginseng® (300 mg/kg/day). Group 4 was orally given Panax Ginseng® at a 300 mg/kg/day dose. Treatments were administered daily and continued for up to 30 consecutive days. Malathion's toxic effect on both hepatic and renal tissues was revealed by a considerable loss in body weight and biochemically by a marked increase in liver enzymes, LDH, ACP, cholesterol, and functional renal markers with a marked decrease in serum TP, albumin, and TG levels with decreased AchE and Paraoxonase activity. Additionally, malondialdehydes, nitric oxide (nitrite), 8-hydroxy-2-deoxyguanosine, and TNFα with a significant drop in the antioxidant activities were reported in the malathion group. Malathion upregulated the inflammatory cytokines and apoptotic genes, while Nrf2, Bcl2, and HO-1 were downregulated. Ginseng® and malathion co-treatment reduced malathion's harmful effects by restoring metabolic indicators, enhancing antioxidant pursuit, lowering the inflammatory reaction, and alleviating pathological alterations. So, Ginseng® may have protective effects against hepatic and renal malathion-induced toxicity on biochemical, antioxidant, molecular, and cell levels.

A dosimetric comparison of Volumetric Modulated Arc Therapy (VMAT) and High Dose Rate (HDR) brachytherapy in localized cervical cancer radiotherapy.

BACKGROUND: Cervical cancer radiotherapy is usually administrated through 3-Dimensional Conformal Radiation Therapy (3DCRT) followed by a brachytherapy (BT) boost. PURPOSE: To investigate whether Volumetric Modulated Arc Therapy (VMAT) can replace High Dose Rate (HDR) intracavitary BT boost for patients undergoing cervical cancer radiotherapy. MATERIALS AND METHODS: Computed Tomography (CT) images for ten patients with tandem and ovoids were included in this study. Target volumes, rectum, bladder, sigmoid, small bowel and both femoral heads were delineated. Two plans were carried out including (a) a BT plan optimized manually by modifying dwell time and Ir-192 source positions, (b) a VMAT plan generated using two partial arcs with 10 MV photon beam. The prescribed dose was 7 Gy. The relevant dose volume parameters (DVPs) of target volumes and OARs for the two plans were analyzed statistically using SPSS Wilcoxon Signed Rank test. RESULTS: VMAT plan showed a significant reduction of 9.1%, 9.3%, 15.4%, 14.4% and 13.1% in rectum maximum dose, rectum D2cc, bladder maximum dose, bladder D2cc and sigmoid maximum dose (P < 0.05). VMAT and BT plans showed comparable D2cc of sigmoid and small bowel maximum doses (P = 0.333 and P = 0.646). On the other hand, VMAT showed significantly higher small bowel D2cc and maximum point dose for both femoral heads comparing to BT plan (P < 0.05). Also, VMAT plan yielded greater homogeneous target coverage compared to BT plan (P < 0.05). CONCLUSION: The study demonstrated that VMAT plan achieves significant dose reduction of rectum, bladder and sigmoid, as well as superior homogeneous target coverage compared to BT plan. On the other hand, VMAT delivers more radiation exposures to small bowel and femoral heads.

The impact of semilateral decubitus position on the dose-volume parameters of the heart and lung for left sided breast cancer patients: A comparative dosimetric study.

PURPOSE: When treating breast cancer with radiation therapy, the impact of treatment position on heart and lung dose-volume parameters (DVPs) is largely dependent on the maximal heart distance (MHD) and central lung distance (CLD). We evaluate how much heart and lung sparing can be achieved using the semilateral decubitus (SLD) position without and with breath hold compared with the standard supine position for left-sided breast cancer patients. A secondary aim was to investigate the impact of MHD and CLD on heart and lung DVPs. METHODS AND MATERIALS: Thirty-five left-sided breast cancer patients were simulated in supine, free breathing SLD, and SLD with breath hold positions. A dosimetry plan was developed for each of these and 3 plans were compared for target coverage and organs at risk sparing. A correlation between CLD, MHD, and planning target volume, and heart and ipsilateral lung DVPs was tested. RESULTS: SLD breath hold position showed a significant reduction in percentage of heart receiving ≥5 Gy (V5Gy), V10Gy, V25Gy, V30Gy, mean dose and maximum dose (P < .001), ipsilateral lung V20Gy, and mean dose compared with supine (P < 001) and free breathing SLD (P = .003 and .006). There was also a significant reduction in the heart DVPs (P < .001) and ipsilateral lung DVPs (P < .001 and .007) with free breathing SLD compared with the supine position. SLD with or without breath hold were associated with significant reduction in MLD (P < .001) and CLD (P = .030 and .003) compared with the supine position. CONCLUSION: Treatment plans for patients in the SLD position with or without breath hold for left-sided breast cancer patients demonstrated a superior heart and lung sparing compared with the supine position due to significant reduction in MHD and CLD. MHD and CLD are important simulation factors that affect the heart and lung DVP.