scholarly journals Apoptosis-Inducing Factor, Protein Expression, and Apoptosis Changes with Glutamine in Podocytes Cells Exposed with Cisplatin

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Imam Susilo ◽  
Himmayatussorofil Maulida ◽  
Lindawati Alimsardjono ◽  
Dyah Fauziah ◽  
Herinda Pertiwi

Cisplatin is a well-known chemotherapeutic drug. It is one of the most effective anticancer agents and is widely used for the treatment of several types of tumors. However, side effects in normal tissues and organs, such as nephrotoxicity that induces apoptosis in epithelial cells in the kidney, limit the use of cisplatin. Glutamine is a substrate for the synthesis of glutathione as an antioxidant and promotes HSP70 release, protecting cells from apoptosis induced by different stimuli. In the present study, we investigated the protective effect of glutamine on cisplatin nephrotoxicity in the kidney. Mice were divided into three groups such as a group of control (P0), a group of intraperitoneal injection of a single dose cisplatin 20 mg/kg BW at 7th day (P1), and a group of intravenous glutamine injection 100 mg/kg BW at days 1–7 and given an intraperitoneal injection of single dose cisplatin 20 mg/kg BW at 7th day (P2). Measurement of AIF expression and apoptotic cells was carried out by immunohistochemical methods. The number of AIF expressions and apoptotic cells is expressed in the Allred score. AIF expression result is as follows: P0: 3.29 ± 0.79, P1: 5.32 ± 0.68, and P2: 4.49 ± 0.47. Apoptosis result is as follows: P0: 3.04 ± 0.70, P1: 5.26 ± 0.53, and P2: 4.44 ± 0.41. There is a decreased expression of AIF on intravenous glutamine administration, followed by a decrease in apoptosis in the podocyte. In conclusion, glutamine administration might represent the treatment of nephrotoxic-induced cisplatin.

2020 ◽  
Vol 26 (40) ◽  
pp. 5174-5187 ◽  
Author(s):  
Abimanyu Sugumaran ◽  
Vishali Mathialagan

Background: The second most common malignant cancer of the uterus is cervical cancer, which is present worldwide, has a rising death rate and is predominant in developing countries. Different classes of anticancer agents are used to treat cervical carcinoma. The use of these agents results in severe untoward side-effects, toxicity, and multidrug resistance (MDR) with higher chances of recurrence and spread beyond the pelvic region. Moreover, the resulting clinical outcome remains very poor even after surgical procedures and treatment with conventional chemotherapy. Because of the nonspecificity of their use, the agents wipe out both cancerous and normal tissues. Colloidal nano dispersions have now been focusing on site-specific delivery for cervical cancer, and there has been much advancement. Methods: This review aims to highlight the problems in the current treatment of cervical cancer and explore the potential of colloidal nanocarriers for selective delivery of anticancer drugs using available literature. Results: In this study, we surveyed the role and potential of different colloidal nanocarriers in cervical cancer, such as nanoemulsion, nanodispersions, polymeric nanoparticles, and metallic nanoparticles and photothermal and photodynamic therapy. We found significant advancement in colloidal nanocarrier-based cervical cancer treatment. Conclusion: Cervical cancer-targeted treatment with colloidal nanocarriers would hopefully result in minimal toxic side effects, reduced dosage frequency, and lower MDR incidence and enhance the patient survival rates. The future direction of the study should be focused more on the regulatory barrier of nanocarriers based on clinical outcomes for cervical cancer targeting with cost-effective analysis.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Katrin Sak

Chemotherapy has been used for cancer treatment already for almost 70 years by targeting the proliferation potential and metastasising ability of tumour cells. Despite the progress made in the development of potent chemotherapy drugs, their toxicity to normal tissues and adverse side effects in multiple organ systems as well as drug resistance have remained the major obstacles for the successful clinical use. Cytotoxic agents decrease considerably the quality of life of cancer patients manifesting as acute complaints and impacting the life of survivors also for years after the treatment. Toxicity often limits the usefulness of anticancer agents being also the reason why many patients discontinue the treatment. The nutritional approach may be the means of helping to raise cancer therapy to a new level of success as supplementing or supporting the body with natural phytochemicals cannot only reduce adverse side effects but improve also the effectiveness of chemotherapeutics. Various plant-derived compounds improve the efficiency of cytotoxic agents, decrease their resistance, lower and alleviate toxic side effects, reduce the risk of tumour lysis syndrome, and detoxify the body of chemotherapeutics. The personalised approach using various phytochemicals provides thus a new dimension to the standard cancer therapy for improving its outcome in a complex and complementary way.


Author(s):  
S.K. Aggarwal ◽  
J. San Antonio

Cisplatin (cis-dichlorodiammineplatinum(II)) a potent antitumor agent is now available for the treatment of testicular and ovarian cancers. It is however, not free from its serious side effects including nephrotoxicity, gastro intestinal toxicity, myelosuppression, and ototoxicity. Here we now report that the drug produces peculiar bloating of the stomach in rats and induces acute ulceration.Wistar-derived rats weighing 200-250 g were administered cisplatin(9 mg/kg) ip as a single dose in 0.15 M NaCl. After 3 days the animals were sacrificed by decapitation. The stomachs were removed, the contents analyzed for pepsin and acidity. The inner surface was examined with a dissecting microscope after a moderate stretching for ulcers. Affected areas were fixed and processed for routine electron microscopy and enzyme cytochemistry.The drug treated animals kept on food and water consistently showed bloating and lesions (Fig. 1) with a frequency of 6-70 ulcers in the rumen section of the stomachs.


2020 ◽  
Vol 24 (5) ◽  
pp. 473-486 ◽  
Author(s):  
Ligia S. da Silveira Pinto ◽  
Thatyana R. Alves Vasconcelos ◽  
Claudia Regina B. Gomes ◽  
Marcus Vinícius N. de Souza

Azetidin-2-ones (β-lactams) and its derivatives are an important group of heterocyclic compounds that exhibit a wide range of pharmacological properties such as antibacterial, anticancer, anti-diabetic, anti-inflammatory and anticonvulsant. Efforts have been made over the years to develop novel congeners with superior biological activities and minimal potential for undesirable side effects. The present review aimed to highlight some recent discoveries (2013-2019) on the development of novel azetidin-2-one-based compounds as potential anticancer agents.


2019 ◽  
Vol 20 (12) ◽  
pp. 1227-1243
Author(s):  
Hina Qamar ◽  
Sumbul Rehman ◽  
D.K. Chauhan

Cancer is the second leading cause of morbidity and mortality worldwide. Although chemotherapy and radiotherapy enhance the survival rate of cancerous patients but they have several acute toxic effects. Therefore, there is a need to search for new anticancer agents having better efficacy and lesser side effects. In this regard, herbal treatment is found to be a safe method for treating and preventing cancer. Here, an attempt has been made to screen some less explored medicinal plants like Ammania baccifera, Asclepias curassavica, Azadarichta indica, Butea monosperma, Croton tiglium, Hedera nepalensis, Jatropha curcas, Momordica charantia, Moringa oleifera, Psidium guajava, etc. having potent anticancer activity with minimum cytotoxic value (IC50 >3μM) and lesser or negligible toxicity. They are rich in active phytochemicals with a wide range of drug targets. In this study, these medicinal plants were evaluated for dose-dependent cytotoxicological studies via in vitro MTT assay and in vivo tumor models along with some more plants which are reported to have IC50 value in the range of 0.019-0.528 mg/ml. The findings indicate that these plants inhibit tumor growth by their antiproliferative, pro-apoptotic, anti-metastatic and anti-angiogenic molecular targets. They are widely used because of their easy availability, affordable price and having no or sometimes minimal side effects. This review provides a baseline for the discovery of anticancer drugs from medicinal plants having minimum cytotoxic value with minimal side effects and establishment of their analogues for the welfare of mankind.


2019 ◽  
Vol 19 (10) ◽  
pp. 765-781
Author(s):  
Seema Rohilla ◽  
Harish Dureja ◽  
Vinay Chawla

Anticancer agents play a vital role in the cure of patients suffering from malignancy. Though, the chemotherapeutic agents are associated with various adverse effects which produce significant toxic symptoms in the patients. But this therapy affects both the malignant and normal cells and leads to constricted therapeutic index of antimalignant drugs which adversely impacts the quality of patients’ life. Due to these adversities, sufficient dose of drug is not delivered to patients leading to delay in treatment or improper treatment. Chemoprotective agents have been developed either to minimize or to mitigate the toxicity allied with chemotherapeutic agents. Without any concession in the therapeutic efficacy of anticancer drugs, they provide organ specific guard to normal tissues.


2019 ◽  
Vol 19 (9) ◽  
pp. 1080-1102 ◽  
Author(s):  
Ghansham S. More ◽  
Asha B. Thomas ◽  
Sohan S. Chitlange ◽  
Rabindra K. Nanda ◽  
Rahul L. Gajbhiye

Background & Objective: :Nitrogen mustard derivatives form one of the major classes of anti-cancer agents in USFDA approved drugs list. These are polyfunctional alkylating agents which are distinguished by a unique mechanism of adduct formation with DNA involving cross-linking between guanine N-7 of one strand of DNA with the other. The generated cross-linking is irreversible and leads to cell apoptosis. Hence it is of great interest to explore this class of anticancer alkylating agents.Methods::An exhaustive list of reviews, research articles, patents, books, patient information leaflets, and orange book is presented and the contents related to nitrogen mustard anti-cancer agents have been reviewed. Attempts are made to present synthesis schemes in a simplified manner. The mechanism of action of the drugs and their side effects are also systematically elaborated.Results::This review provides a platform for understanding all aspects of such drugs right from synthesis to their mechanism of action and side effects, and lists USFDA approved ANDA players among alkylating anticancer agents in the current market.Conclusion: :Perusing this article, generic scientists will be able to access literature information in this domain easily to gain insight into the nitrogen mustard alkylating agents for further ANDA development. It will help the scientific and research community to continue their pursuit for the design of newer and novel heterocyclic alkylating agents of this class in the coming future.


2020 ◽  
Vol 20 (11) ◽  
pp. 1288-1299
Author(s):  
Paromita Kundu ◽  
Deepika Singh ◽  
Abhalaxmi Singh ◽  
Sanjeeb K. Sahoo

The panorama of cancer treatment has taken a considerable leap over the last decade with the advancement in the upcoming novel therapies combined with modern diagnostics. Nanotheranostics is an emerging science that holds tremendous potential as a contrivance by integrating therapy and imaging in a single probe for cancer diagnosis and treatment thus offering the advantage like tumor-specific drug delivery and at the same time reduced side effects to normal tissues. The recent surge in nanomedicine research has also paved the way for multimodal theranostic nanoprobe towards personalized therapy through interaction with a specific biological system. This review presents an overview of the nano theranostics approach in cancer management and a series of different nanomaterials used in theranostics and the possible challenges with future directions.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Safa Najafi ◽  
Maryam Ansari ◽  
Vahid Kaveh ◽  
Shahpar Haghighat

Abstract Background The objective of this study was to compare the efficacy and side effects of a single dose (Pegfilgrastim or PDL) or repeated six daily injections (Filgrastim or PDG) during chemotherapy courses in breast cancer patients in a non-inferiority clinical trial. Methods In this randomized clinical trial, 80 patients were recruited and allocated randomly to two equal arms. In one group, a single subcutaneous dose of PDL was injected the day after receiving the chemotherapy regimen in each cycle. The second arm received a subcutaneous injection of PDG for six consecutive days in each cycle of treatment. The side effects of GCF treatment and its effect on blood parameters were compared in each cycle and during eight cycles of chemotherapy. Results Hematologic parameters showed no significant differences in any of the treatment courses between the two study groups. The comparison of WBC (p = 0.527), Hgb (p = 0.075), Platelet (p = 0.819), Neutrophil (p = 0.575), Lymphocyte (p = 705) and ANC (p = 0.675) changes during the eight courses of treatment also revealed no statistically significant difference between the two study groups. Side effects including headache, injection site reaction and muscle pain had a lower frequency in patients receiving PDL drugs. Conclusion It seems that PDL is non-inferior in efficacy and also less toxic than PDG. Since PDL can be administered in a single dose and is also less costly, it can be regarded as a cost-effective drug for the treatment of chemotherapy-induced neutropenia. Trial registration IRCT20190504043465N1, May 2019.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Masashi Arita ◽  
Satoshi Watanabe ◽  
Nobumasa Aoki ◽  
Shoji Kuwahara ◽  
Ryo Suzuki ◽  
...  

AbstractCisplatin, one of the most active anticancer agents, is widely used in standard chemotherapy for various cancers. Cisplatin is more poorly tolerated than other chemotherapeutic drugs, and the main dose-limiting toxicity of cisplatin is its nephrotoxicity, which is dose-dependent. Although less toxic methods of cisplatin administration have been established, cisplatin-induced nephrotoxicity remains an unsolved problem. Megalin is an endocytic receptor expressed at the apical membrane of proximal tubules. We previously demonstrated that nephrotoxic drugs, including cisplatin, are reabsorbed through megalin and cause proximal tubular cell injury. We further found that cilastatin blocked the binding of cisplatin to megalin in vitro. In this study, we investigated whether cilastatin could reduce cisplatin-induced nephrotoxicity without influencing the antitumor effects of cisplatin. Nephrotoxicity was decreased or absent in mice treated with cisplatin and cilastatin, as determined by kidney injury molecule-1 staining and the blood urea nitrogen content. Combined with cilastatin, a twofold dose of cisplatin was used to successfully treat the mice, which enhanced the antitumor effects of cisplatin but reduced its nephrotoxicity. These findings suggest that we can increase the dose of cisplatin when combined with cilastatin and improve the outcome of cancer patients.


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