Cisplatin Group Research Articles

Nano Spirulina platensis countered cisplatin-induced repro-toxicity by reversing the expression of altered steroid hormones and downregulation of the StAR gene.

Cisplatin is a commonly utilized chemotherapy medication for treating different sarcomas and carcinomas. Its ability interferes with cancer cells' DNA repair pathways and postpones unfavorable outcomes in cancer patients. The current investigation's goal was to ascertain if nano Spirulina platensis (NSP) might shield rat testicles from cisplatin damage by assessing the expression of the StAR and SOD genes, sex hormones, 17ß-hydroxysteroid dehydrogenase(17ß-HSD), sperm profile picture, oxidative condition of testes, testicular histology, and DNA damage. Four equal and random groups of 28 adult male Wistar rats were created; the control group was given saline for 8weeks. An extraction of NSP at a concentration of 2500mg/kg body weight was administered orally for 8weeks to the NSP group. For the first 4weeks, the cisplatin group was intraperitoneally injected with 2mg/kg/body weight of cisplatin, and for the next 4weeks, they were given a dosage of 4mg/kg/body weight. The cisplatin + NSP group was given both NSP and cisplatin. The results of the experiment showed that intake of NSP and cisplatin improved sperm profile; re-established the balance of oxidizing agents and antioxidant state; enhanced testicular histology; promoted the histometric parameters of seminiferous tubules including epithelial height, their diameter, and Johnsen's score, decreasing DNA breakage in testicular tissue; increased testosterone level; decreased 17ß-HSD concentration; and upregulated both the StAR and SOD gene expression in testicles compared to rats exposed to cisplatin alone. These results demonstrate that NSP is a promising agent for improving cisplatin-induced testicular injury and infertility.

AptBCis1, An Aptamer-Cisplatin Conjugate, Is Effective in Lung Cancer Leptomeningeal Carcinomatosis.

Treatment of lung cancer leptomeningeal carcinomatosis (LM) remains challenging partly due to the biological nature of the blood-brain barrier (BBB). Cisplatin has limited effects on LM, and it is notorious for neurotoxicity. Aptamers are small oligonucleotides considered as antibody surrogates. Here we report a DNA therapeutics, AptBCis1. AptBCis1 is a cisplatin-conjugated, BBB-penetrating, and cancer-targeting DNA aptamer. Its backbone, AptB1, was identified via in vivo SELEX using lung cancer LM orthotopic mouse models. The AptB1 binds to EAAT2, Nucleolin, and YB-1 proteins. Treatment with AptBCis1 1 mg/kg (equivalent to cisplatin 0.35 mg/kg) showed superior tumor suppressive effects compared to cisplatin 2 mg/kg in mice with lung cancer LM diseases. The cerebrospinal fluid platinum concentration in the AptBCis1 group was 10% of that in the cisplatin group. The data suggested the translational potential of AptBCis1 in lung cancer with LM and in cancers in which platinum-based chemotherapy remains as the standard of care.

Engineering of Kidney-Targeting Fluorophores with Tunable Emission from NIR-I to NIR-II for Early Diagnosis of Kidney Disease.

The development of rapidly distributed and retained probes within the kidneys is important for accurately diagnosing kidney diseases. Although molecular imaging shows the potential for non-intrusively interrogating kidney disease-related biomarkers, the limited kidney contrast of many fluorophores, owing to their relatively low distribution in the kidney, hinders their effectiveness for kidney disease detection. Herein, for the first time, an amino-functionalization strategy is proposed to construct a library of kidney-targeting fluorophores NHcy with tunable emissions from NIR-I to NIR-II. Among these, NHcy-8 is the first small-molecule NIR-II dye without a renal clearance moiety, designed specifically for kidney-targeting imaging. Building on this class of NIR-II fluorophore, the first NIR-II small-molecule kidney-targeting pH probe NIR-II-pH is developed, which exhibits a desirable kidney distribution after intravenous injection and is fluorescent only after activation by acidosis. NIR-II in vivo fluorescence/photoacoustic imaging of kidney disease models induced by cisplatin and renal I/R injury using NIR-II-pH reveals increasingly severe metabolic acidosis as the disease progressed, enabling sensitive detection of the onset of acidosis 36h (cisplatin group) earlier than clinical methods. Thus, this study introduces a practical NIR-II kidney-targeting probe and provides a useful molecular blueprint for guiding kidney-targeting NIR-II fluorophores as diagnostic aids for kidney diseases.

Nephroprotective Activity of Angelica keiskei (Miq). Koidz. on Cisplatin-Induced Rats: Reducing Serum Creatinine, Urea Nitrogen, KIM-1, and Suppressing NF-kappaB p65 and COX-2.

The sap of Angelica keiskei (Miq). Koidz. has been reported for its abundance of chalcone contents. Chalcones have been known for their effective nephroprotective activity toward cisplatin-induced renal cells and mice. To investigate the effect of A. keiskei sap extract (ASEE) on kidney function parameters (serum creatinine, urea nitrogen, and kidney injury molecule-1) and the expression of NF-kappaB p65 and COX-2 in cisplatin-induced Wistar rats. In vivo nephroprotective activity of ASEE at 1000 and 1500 mg/kg BW/day doses for 10 days on cisplatin (5 mg/kg BW) induced nephrotoxicity was evaluated on Wistar rats. Quercetin 20 mg/kg BW/day was used as the control drug. Cisplatin inducement was given on day 7. The BW was measured every day. On day 11, the rats were euthanized, and their blood was taken intracardially for creatinine and urea nitrogen analysis. Histopathological analysis was carried out on the right kidney, and KIM-1 levels in the left kidney were measured. The Western blot technique evaluated the NF-kappaB p65 and COX-2 expression in the kidney. All data obtained were compared to the cisplatin group (negative control). The total flavonoids and chalcones in ASEE were also determined. Pretreatment with ASEE reduces the BW of Wistar rats, and significantly reduces creatinine and KIM-1 levels, but does not significantly reduce the levels of urea nitrogen, the expression of NF-kappaB p65, and COX-2 in the kidney of cisplatin-induced Wistar rats. The total flavonoid content in ASEE is 8.755 g QE/100 g extract and the total chalcone content is 5.532 g IBCE/100 g extract. The sap of Angelica keiskei (Miq). Koidz. reveal the potential to protect the kidneys against cisplatin-induced toxicity. The nephroprotective activity may be attributed to the antioxidant and anti-inflammatory properties of the flavonoids and the chalcones contained in the sap of Angelica keiskei (Miq). Koidz.

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

The study aims to examine the possible effect of melatonin against cisplatin-induced submandibular degeneration in experimental rats exploring its ameliorative mechanisms. 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. The results indicate that intraperitoneal administration of melatonin (30 mg/kg body weight) alongsidecisplatin significantly elevated submandibular glands (SMG) and reduced glutathione (GSH) and superoxide dismutase (SOD) levels (p < 0.001), while it reducedmalondialdehyde (MDA) levels, NF-κB gene expression, the protein level of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), 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. 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.

The Hepatoprotective Effects of Camellia sinensis on Cisplatin-Induced Acute Liver Injury.

Acute liver injury is an increasing global health problem. It is a widespread side effect of cisplatin treatment in the clinic and can lead to liver failure if not treated promptly. Previous studies have revealed that green tea can protect some organs from treatments. However, the potential of white tea to prevent the negative effects of acute liver injury has not been addressed so far. The purpose of this study was to investigate the reduction in cisplatin-induced liver injury in rats receiving white tea. Female Sprague Dawley rats with similar weight were selected in this study. Twenty-four rats were divided into three groups of eight animals each and ad libitum nutrition was provided. The control and cisplatin groups were given tap water only, while the white tea + cisplatin group received white tea at a 0.5% weight/volume concentration for four weeks. At the end of the fourth week, the white tea + cisplatin group and the cisplatin group received a single dose of cisplatin (7 mg/kg) via the intraperitoneal route. Five days after that procedure, the rats were anesthetized. Liver tissues and blood samples were collected, which were used for biochemical and histopathological analyses. According to biochemical results, liver tissue MDA and GSH, serum ALT, and AST levels significantly increased in the cisplatin group compared to the control group. Compared with the cisplatin group, although MDA, AST, ALT, and GSH levels were lower in the white tea + cisplatin group, only GSH levels were statistically different. The examination of histopathological and immunohistochemical findings revealed apoptotic cells, vascular congestion, and sinusoidal dilatation in the cisplatin group compared to the control group. This adverse event decreased in the white tea + cisplatin group compared to the cisplatin group. In conclusion, white tea exhibits an ameliorating effect on cisplatin-induced liver injury.

Galaxamide alleviates cisplatin-induced premature ovarian insufficiency via the PI3K signaling pathway in HeLa tumor-bearing mice

BackgroundIt is challenging to improve the effects of chemotherapy and reduce its adverse impact on the ovaries. Our previous study suggested that the combination of galaxamide could enhance the antitumor effect of cisplatin (CIS) in HeLa cell xenograft mice. However, their potential effects on ovarian tissues remain unknown.MethodsThe Hela tumor-bearing female BALB/c mice model was established and randomly divided into three groups: control group (PBS group), CIS group (0.3 mg/kg CIS group) and galaxamide group (0.3 mg/kg CIS + 3 mg/kg galaxamide-treated group). The serum sex hormones levels, ovarian morphology, functional and molecular characterisation were determined and compared with those of the control group.ResultsThe hormonal effects indicated premature ovarian insufficiency (POI) associated with CIS-induced tumor-bearing mice. CIS induces the apoptosis in primordial and developing follicles and subsequently increases follicular atresia, eventually leading to follicle loss. After cotreatment, galaxamide significantly increased anti-Mullerian hormone (AMH) and follicle-stimulating hormone receptor (FSHR) expression and prevented the CIS-induced PI3K pathway, which triggers follicle activation, apoptosis or atresia.ConclusionThese findings demonstrate that galaxamide could attenuate CIS-induced follicle loss by acting on the PI3K signaling pathway by stimulating AMH and/or FSHR and thus provides promising therapeutic options for patients with cervical cancer.

The significance of consolidation chemotherapy after concurrent chemoradiotherapy in esophageal squamous cell carcinoma: a randomized controlled phase III clinical trial.

This study explored the significance of consolidation maintenance chemotherapy after concurrent chemoradiotherapy with different regimens in patients with esophageal squamous cell carcinoma. A prospective randomized controlled phase III clinical trial was designed and registered in the China Clinical Trials Registry (Registration number: ChiCTR-TRC-12002719). Survival data were analyzed in terms of intention-to-treat (ITT) and per-protocol (PP) sets for patients undergoing cisplatin and 5-fluorouracil (PF) (group A), or cisplatin and paclitaxel (TP) (group B). The incidence risk of grade III-IV leukopenia in group B was higher than in group A (49.2% vs. 25.5%, p = 0.012). The survival rates at 1, 2, 3, and 5 years were 83.8%, 62.6%, 53.1%, and 41.3%, respectively. Consolidation chemotherapy after concurrent chemoradiation therapy had no benefit on median progression-free survival (PFS) (p = 0.95) and overall survival (OS) (p = 0.809). According to the ITT analysis, the median PFS in group A and group B was 28.6 months and 30.3 months (X2 = 0.242, p = 0.623), while the median OS was 31.0 months and 50.3 months (X2 = 1.25，p = 0.263). For the PP analysis, the median PFS in group A and group B were 28.6 months and 30.3 months (p = 0.584), while the median OS was 31.0 months and 50.3 months (p = 0.259), respectively. Patients receiving consolidation chemotherapy did not show significant OS benefits (46.9 months vs. 38.3 months; X2 = 0.059, p = 0.866). Similar PFS and OS were found between PF and TP regimens with concurrent chemoradiotherapy. Consolidation chemotherapy did not show any significant OS benefits.

Protective effect of hydroethanolic leaves extract of Solanum macrocarpon on Cisplatin-induced kidney injury in rats

Background: Nephrotoxicity is a common kidney condition affecting many people worldwide, with conventional synthetic drugs not often yielding desirable results. This study, therefore, aimed to assess the protective effect of Solanum macrocarpon on Cisplatin-induced nephrotoxicity in Wistar rats. Methods: Hydroethanolic extract of the leaves of S. macrocarpon was prepared and analyzed for basic phytochemical constituents. Cisplatin (5 mg/kg) was administered to induce nephrotoxicity. The extract was administered at 100, 250, and 500 mg/kg for 10 days, and Silymarin standard (120 mg). After 10 days, the rats were sacrificed, and their blood samples and kidneys were collected for biochemical, hematological, and histopathological analyses. Results: The extract was rich in flavonoids, coumarins, terpenoids, and tannins. The serum levels of urea and creatinine were significantly higher in the cisplatin group compared to the normal group. However, in the extract co-administered groups, there was a reduction in the urea and creatinine levels relative to the cisplatin-only group. The kidney microarchitecture also improved with the administration of the extract. Conclusion: S. macrocarpon extract was effective in treating acute nephrotoxicity caused by cisplatin at the microarchitectural level of kidneys. This protective effect might be attributed to the phytochemical constituents. The extract's 250mg/kg dose showed the best nephroprotective ability. Keywords: Nephrotoxicity, Solanum macrocarpon, Kidneys, Cisplatin, Creatinine, Urea.

Effect of short-term fasting on the cisplatin activity in human oral squamous cell carcinoma cell line HN5 and chemotherapy side effects

BackgroundKetogenic interventions like short-term fasting show potential as complementary therapies to enhance the effectiveness of chemotherapy for cancer. However, the specific effects of fasting on head and neck squamous cell carcinoma (HNSCC) cells and healthy oral mucosa cells during these treatments are not well understood. This study investigates whether short-term fasting can differentially impact HNSCC cell survival and viability compared to healthy keratinocytes while undergoing standard chemotherapy regimens.MethodsThis study investigated the effects of fasting on cell viability in HN5 cell line and healthy oral keratinocyte cells. The HN5 cell line, derived from human tongue squamous cell carcinoma, and primary human keratinocytes isolated from the basal layer of gingival epithelium were divided into three groups: (1) control, (2) treated with the standard chemotherapeutic agent cisplatin, and (3) treated with cisplatin under fasting conditions achieved through 48-hour glucose restriction mimicking the blood glucose levels of fasted individuals. Cell proliferation was assessed at 48 and 72 h using the MTT assay, a colorimetric method based on mitochondrial dehydrogenase activity. Flow cytometry analysis with specific apoptosis and necrosis markers distinguished between early and late apoptotic, necrotic, and viable cells.ResultsCell viability in HN5 and healthy keratinocyte cells decreased in cisplatin with low glucose groups compared to cisplatin and control groups. The same results were observed for healthy keratinocyte cells; only a decrease in cell viability in cisplatin groups compared to control groups was observed, which was not statistically significant. Cell apoptosis in HN5 and healthy keratinocyte cells increased in cisplatin with low glucose groups compared to cisplatin and control groups. In healthy keratinocyte cells, the cisplatin with low glucose group showed an impressive increase in necrosis, late apoptosis, and early apoptosis and a significant decrease in live cells compared with other groups.ConclusionThis study revealed that short-term fasting chemotherapy significantly improved HNSCC cell line apoptosis and necrosis.

Immediate intratesticular injection of circulating blood serum-derived exosomes may alleviate orchitis caused by cisplatin

Objective: Cisplatin (CIS), as a common chemotherapy drug, induces detrimental effects on the testis. Besides, exosomes represent various beneficial effects, such as anti-inflammation and proliferation. In this experimental study, the authors aimed to evaluate the anti-inflammatory effects of circulating blood serum-derived exosomes on orchitis caused by CIS exposure. Methods: Male mice (n=18) were categorized into three main groups: control (no treatment), CIS (mice with orchitis caused by CIS injection), and CIS+Exosome (orchitis-induced animals followed by exosome treatment). Exosomes were extracted from circulating blood, and orchitis was induced by intraperitoneal injection of CIS (7.5mg/kg/day) for 5 consequence days. A day after the last dose of CIS, the exosome (10IU/20grmice) was injected intratesticularly. After a week, the samples, including blood serum and testis, were gathered. The levels of oxidative stress were assessed using Malondialdehyde (MDA) and nitric oxide (NO) assays. Sperm parameters (morphology, viability, motility, and count), testosterone levels, and inflammatory (TNF-α, IL-6, and IL-10) gene expression were also evaluated. Histopathological and testicular apoptotic index (AI) were evaluated using H&amp;E and TUNEL stainings, respectively. Finally, data analysis was applied by SPSS (v.19) software, and P&lt;0.05 was considered as a significant level. Results: Following CIS administration, the sperm indices and testosterone levels were decreased (P&lt;0.05); besides, NO, MDA, AI, and inflammatory gene expression were increased (P&lt;0.05) in the CIS group compared to control animals. Following the prescription of Exosomes in CIS animals, the sperm indices and testosterone levels were increased (P&lt;0.05), and NO, MDA, AI, and inflammatory genes were decreased (P&lt;0.05). Histopathological assessments also revealed disruption of seminiferous tubules and free from sperms following CIS administration. Also, the histological structure of damaged seminiferous tubules was changed to normal status following Exoxome prescription in CIS-exposure animals. Conclusion: Immediate intratesticular injection of blood-derived exosomes can alleviate orchitis CIS-exposed animals through anti-inflammatory features.

Comparison of First-Line Chemotherapeutics and Validation of the EORTC Prognostic Index in Malignant Pleural Mesothelioma: Retrospective Single-Centre Experience.

To evaluate the efficiency of pemetrexed cisplatin in comparison with gemcitabine cisplatin and to validate the EORTC (European Organisation for Research and Treatment of Cancer) prognostic score in combination chemotherapy treatment for malignant pleural mesothelioma. An observational study. Place and Duration of the Study:Department of Oncology, Dicle University Hospital, Diyarbakir, Turkiye, from October 2000 to November 2017. Malignant pleural mesothelioma (MPM) patients with EORTC score 0- were recruited. Factors affecting the prognosis of the disease and the effectiveness of first-line treatment were retrospectively analysed. EORTC prognostic score was calculated with a cut-off and survival analyses were used by the Kaplan-Meier method. Log-rank and univariable Cox regression tests were used to search for prognostic factors' impact on survival. Patients who received gemcitabine cisplatin treatment had a median progression-free survival (PFS) of 9 months, while those who received pemetrexed cisplatin therapy had a median PFS of 7 months. Median overall survival (OS) was 17 months in the gemcitabine cisplatin group and 18 months in the pemetrexed cisplatin group (p = 0.051). When the low-risk group was compared with the high-risk group, the median OS was found to be statistically significant (p = 0.009). The EORTC prognostic score, which is used for prognostic prediction in the period when pemetrexed is not utilised in the treatment of MPM, accurately predicts prognosis subsequent to the administration of pemetrexed in treatment. In the context of first-line treatment, cisplatin in combination with gemcitabine and cisplatin in combination with pemetrexed demonstrated comparable efficacy with respect to both overall survival and progression-free survival. Chemotherapy, Mesothelioma, Prognosis, Gemcitabine, Progression-free survival.

VALD-2 mitigates cisplatin-induced acute kidney injury: Mechanistic insights into oxidative stress modulation and inflammation suppression.

This study explores the compelling antitumor properties of VALD-2, a synthetic Schiff base ligand known for its low toxicity. The focus is on investigating VALD-2's protective role against cisplatin-induced acute kidney injury (AKI) in mice, with a specific emphasis on mitigating oxidative stress and inflammation. The study involves daily intraperitoneal injections of amifostine or VALD-2 over 7 days to establish an AKI model. Subsequently, mice were assigned to normal control, cisplatin group, cisplatin + amifostine group, and cisplatin + VALD-2 10 mg/kg group, cisplatin + VALD-2 20 mg/kg, and cisplatin + VALD-2 40 mg/kg. Kidney injury is assessed through serum blood urea nitrogen (BUN) and creatinine (Cr) activity assays. Levels of inflammatory factors,tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), in kidney tissue of mice were assessed through enzyme-linked immunosorbent assay (ELISA). The protective effect of VALD-2 is further examined through HE staining to observe pathological changes in kidney injury. The ultrastructural changes of renal cells and tubular epithelial cells were observed by electron microscopy under experimental conditions, indicating the effect of VALD-2 on reversing cisplatin-induced renal injury. The study delves into VALD-2's protective mechanisms against cisplatin-induced kidney injury by using western blot analysis to assess the expression levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) in kidney tissues. VALD-2 demonstrates significant improvement in cisplatin-induced AKI, as evidenced by increased BUN and Cr levels. It effectively protects kidney tissue from oxidative damage, enhancing SOD and GSH-Px activities while reducing MDA levels. The study also reveals a decrease in TNF-α and IL-6 levels, supported by ELISA results, and histological findings confirm anti-nephrotoxic effects. Western blot analysis shows an upregulation of antioxidant enzymes (SOD, GSH-Px) and a reduction in MDA production. VALD-2 emerges as a promising mitigator of cisplatin-induced AKI, showcasing its ability to enhance oxidative stress-related protein expression. The findings suggest VALD-2 as a potential therapeutic agent for protecting against cisplatin-induced kidney injury.

Co-administration of either curcumin or resveratrol with cisplatin treatment decreases hepatotoxicity in rats via anti-inflammatory and oxidative stress-apoptotic pathways.

Cisplatin (CIS) is a broad-spectrum anticancer drug, with cytotoxic effects on either malignant or normal cells. We aimed to evaluate the hepatotoxicity in rats caused by CIS and its amelioration by the co-administration of either curcumin or resveratrol. Forty adult male rats divided into four equal groups: (control group): rats were given a saline solution (0.9%) once intraperitoneally, daily for the next 28 days; (cisplatin group): rats were given a daily oral dose of saline solution (0.9%) for 28 days after receiving a single dose of cisplatin (3.3 mg/kg) intraperitoneally for three successive days; (CIS plus curcumin/resveratrol groups): rats received the same previous dose of cisplatin (3.3 mg/kg) daily for three successive days followed by oral administration of either curcumin/resveratrol solution at a dose of (20 mg/kg) or (10 mg/kg) consequently daily for 28 days. Different laboratory tests (ALT, AST, ALP, bilirubin, oxidative stress markers) and light microscopic investigations were done. Administration of CIS resulted in hepatotoxicity in the form of increased liver enzymes, oxidative stress markers; degenerative and apoptotic changes, the co-administration of CIS with either curcumin or resveratrol improved hepatotoxicity through improved microscopic structural changes, reduction in liver enzymes activity, decreased oxidative stress markers, improved degenerative, and apoptotic changes in liver tissues. Co-administration of either curcumin or resveratrol with cisplatin treatment could ameliorate hepatotoxicity caused by cisplatin in rats via anti-inflammatory and oxidative stress-apoptotic pathways.

Protective and therapeutic effects of nobiletin against cisplatin-induced nephrotoxicity in rats

ABSTRACT Possible protective and therapeutic effects of nobiletin on kidney in a cisplatin-induced nephrotoxicity rat model were investigated. Forty male albino rats were divided into four groups: control, cisplatin (CIS), cisplatin+nobiletin (CIS+NOB), and nobiletin+cisplatin (NOB+CIS). At the end of the study, the rats were subjected to biochemical, histological and immunohistochemical analyzes. Compared to the control group, tGSH (p < 0.05) levels, and G6PD (p < 0.05) and GPx (p < 0.001) activities, were increased in the CIS group; while significant (p < 0.05) decreases occurred in the MDA and TOC levels. Histopathologically, the kidneys of the groups administered nobiletin (CIS+NOB, NOB+CIS) were significantly different from the CIS group, being closer to control group in terms of degeneration and hyaline cylinder formation in the tubules (p < 0.05). While dilatation in the tubules, protein-rich fluid and hyaline cylinder formation in the lumen were most common in the CIS group, a significant decrease (p < 0.05) of these parameters was seen in the nobiletin groups (CIS+NOB, NOB+CIS). This study suggests that nobiletin can be effective in preventing and ameliorating toxic effects of cisplatin on the kidney.

Dihydromyricetin Inhibits Ferroptosis to Attenuate Cisplatin-Induced Muscle Atrophy.

Cisplatin is a widely used chemotherapy drug for the treatment of various cancers. However, although cisplatin is effective in targeting cancer cells, it has severe side effects including skeletal muscle atrophy. In this study, we aimed to characterize the role of Dihydromyricetin in cisplatin-induced muscle atrophy in mice. 5-week-old male C57BL/6 mice were treated with Dihydromyricetin for 14 days orally followed by in intraperitoneally cisplatin administration for 6 days. Gastrocnemius muscles were isolated for the following experiments. Antioxidative stress were determined by peroxidative product malondialdehyde (MDA) and antioxidants superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Quadriceps muscle mass and grip strength were significantly restored by Dihydromyricetin in a dose-dependent manner. Moreover, muscle fibers were improved in Dihydromyricetin treated group. Excessive skeletal muscle E3 ubiquitin-protein ligases in cisplatin group were significantly repressed by Dihydromyricetin treatment. Dihydromyricetin significantly reduced oxidative stress induced by cisplatin by decreasing MDA level and restored SOD and GPx activities. In addition, ferroptosis was significantly reduced by Dihydromyricetin characterized by reduced iron level and ferritin heavy chain 1 and improved Gpx4 level. The present study demonstrated that Dihydromyricetin attenuated cisplatin-induced muscle atrophy by reducing skeletal muscle E3 ubiquitin-protein ligases, oxidative stress, and ferroptosis.

Structural Elucidation and Anti-Tumor Activity of a Polysaccharide (CP2-S) from Cordyceps militaris Fruit Bodies.

A polysaccharide (CP2-S), consisting of glucose with a weight average molecular weight of 5.9 × 106, was purified from the fruit bodies of Cordyceps militaris. In this work, the corresponding structure and anti-tumor activity in vivo were investigated. Methylation and NMR analysis revealed that CP2-S was composed of a →4)-α-D-Glcp-(1→ backbone with partial substitution occurring at O-6 by T-linked α-D-Glcp in every ten residues, which has not been reported in previous reports. In vivo anti-tumor experiments showed that CP2-S could inhibit the growth of Lewis lung carcinoma in mice. Tumor inhibition rates were 17.8%, 24.5%, and 29.5% at dosages of 12.5, 50, and 100 mg/kg/d, respectively. Compared with the cisplatin group, mice treated with CP2-S exhibited a significant increase in spleen index (increased 22.7-42.4%) and thymus index (increased 47.7-36.8%). Additionally, serum levels of IgM and IgG in tumor-bearing mice increased by approximately 6.11~10.75-folds and 1.31~1.38-folds, respectively. These findings prove that CP2-S significantly inhibited the growth of Lewis lung carcinoma through immune-enhancing activity in mice.

Protective role of apigenin nanoparticles in cisplatin induced cardiotoxicity in rats

Purpose This study aims to assess the effect of both apigenin-loaded zinc oxide nanoparticles (ZnONPs) and apigenin only against cisplatin (CP)-induced experimental cardiotoxicity. Design/methodology/approach A total of 32Wister rats (male) were randomly divided (n = 8) into four groups. Normal control group, CP group received CP (20 mg/kg); treated group I received CP and then received apigenin (0.78 mg/kg/day) orally; treated group II received CP and then received apigenin loaded ZnONPs. At the end of the experiment (10 days), samples were extracted from each rat for the assessment of complete blood picture, lipid profile, atherogenic indices, oxidative status, inflammatory and cardiotoxicity markers as well as histological examination. Findings The results indicated that CP produced significant alterations in the complete blood picture, lipidemic profile, atherogenic indices, antioxidation capacity and cardiac inflammatory markers as well as function enzymes as compared with the control group. Administration of apigenin only showed a non-significant change in the atherogenic indices, oxidative status and cardiotoxicity parameters, indicating incomplete cardio-protection against CP upon. Additionally, all the observed alterations in CP group were reversed when apigenin nanoparticle at lower dose was used with ZnONPs which was also confirmed by histopathological investigation. Originality/value The apigenin loaded ZnONPs exert protective effects against CP-induced experimental cardiotoxicity and improved cardiac function, suggesting a potential adjuvant role of apigenin nanoparticles against cardiotoxicity.

Juzentaihoto alleviates cisplatin‐induced renal injury in mice

AbstractAimCisplatin is a highly effective anti‐cancer agent, but its clinical use is restricted due to severe renal toxicity. This study aimed to investigate the alleviative effects of juzentaihoto (JTT) in a mouse model of cisplatin‐induced renal injury.MethodsFour groups of seven‐week‐old male C57BL/6J mice (control, JTT, cisplatin, and JTT + cisplatin groups) were used in the study. The JTT and JTT + cisplatin groups received oral JTT (500 mg/kg) once a day for three days. After 24 h, the cisplatin, and JTT + cisplatin groups were intraperitoneally injected with cisplatin (15 mg/kg). The mice in each group were euthanized 72 h after cisplatin administration, and blood and kidney samples were collected.ResultsCisplatin injection decreased body weight and elevated plasma blood urea nitrogen and creatinine levels, while also increasing renal oxidative stress, inflammation, and cell death. These changes were alleviated by JTT administration. We also found that platinum accumulation in the kidneys following cisplatin injection was attenuated by JTT treatment. Furthermore, Mate1 expression levels (a cisplatin efflux transporter) were upregulated by JTT injection.ConclusionOur results demonstrated that JTT mitigated cisplatin‐induced renal injury in mice by alleviating oxidative stress, inflammation, and cell death, achieved through the upregulation of the cisplatin efflux transporter Mate1.

A Comparative Histological Study Between the Protective and the Therapeutic Effect of Probiotic on Cisplatin Induced Nephrotoxicity in Adult Male Albino Rat

Abstract Introduction Although cisplatin (CP) is one of the most effective chemotherapies, it is associated with significant nephrotoxicity (Acute kidney injury). Lactobacillus plantarum is often used as a probiotic on its own for its beneficial properties and anti-inflammatory activity. Aim to compare the protective and therapeutic role of probiotics on the microscopic structure of the kidney in a model of cisplatin-induced nephrotoxicity. Material and Methods thirty-five adult male albino rats weighing (200-220gm) were divided into 4 groups. Group I (control group), Group II (Cisplatin group): rats received intraperitoneal injection of CP (7.5 mg/kg) for 3 days. Group III (protective group): Rats received 1 mL of probiotic orally for 7 days. From the fifth day, the rats received intraperitoneal injections of CP (7.5mg/kg) for 3 days. Group IV (Therapeutic group): Rats received intraperitoneal injection of CP for 3 days. From the fourth day, the rats received probiotic L. plantarum orally at a dose of (1 mL/day) for 14 days. The concentration of probiotics in group III and group IV was 109 Colony forming units (CFU)/mL/100 g of body weight. Kidney specimens were proceeded for light microscopic examination, as well as Morphometrical and statistical analyses. Results H&amp;E-stained sections of Group II showed marked renal affection in which most glomeruli showed atrophy. Renal tubules were mostly distorted, necrotic, and degenerative with interstitial hemorrhage, congestion, and cellular infiltration. PAS-stained sections showed marked increased reaction in glomerular and tubular Basement membranes with an apparent loss of Brush borders of most of the PCTs. Masson`s trichrome-stained sections showed a marked increase in collagen fibers in renal interstitia mostly around blood vessels. Immunohistochemically stained sections showed a marked increase in positive cytoplasmic reaction to caspase -3 antibodies mostly in renal tubules. On the other hand, the renal structure of The protective group showed marked improvement which appeared nearly comparable to that of the control group while the therapeutic group showed minimal improvement. Conclusion The protective effect of probiotics on cisplatin-induced Acute Kidney Injury (Nephrotoxicity) was markedly better than the therapeutic effect as detected by microscopic, morphometric, and statistical studies.