Liposomal Ellagic Acid Alleviates Cyclophosphamide-Induced Toxicity and Eliminates the Systemic <i>Cryptococcus neoformans</i> Infection in Leukopenic Mice
<i>Cryptococcus neoformans</i> infections rose sharply due to rapid increase in the numbers of immunocompromised individuals in recent years. Treatment of Cryptococcosis in immunocompromised persons is largely very challenging and hopeless. Hence, this study aimed to determine the activi...
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MDPI AG
2021-06-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/6/882 |
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| author | Masood Alam Khan Arif Khan Mohd Azam Khaled S. Allemailem Faris Alrumaihi Ahmad Almatroudi Fahad A. Alhumaydhi Faizul Azam Shaheer Hasan Khan Syeda Fauzia Farheen Zofair Sumbul Ahmad Hina Younus |
| author_facet | Masood Alam Khan Arif Khan Mohd Azam Khaled S. Allemailem Faris Alrumaihi Ahmad Almatroudi Fahad A. Alhumaydhi Faizul Azam Shaheer Hasan Khan Syeda Fauzia Farheen Zofair Sumbul Ahmad Hina Younus |
| author_sort | Masood Alam Khan |
| collection | DOAJ |
| description | <i>Cryptococcus neoformans</i> infections rose sharply due to rapid increase in the numbers of immunocompromised individuals in recent years. Treatment of Cryptococcosis in immunocompromised persons is largely very challenging and hopeless. Hence, this study aimed to determine the activity of ellagic acid (EA) in the treatment of <i>C. neoformans</i> in cyclophosphamide injected leukopenic mice. A liposomal formulation of ellagic acid (Lip-EA) was prepared and characterized, and its antifungal activity was assessed in comparison to fluconazole (FLZ). The efficacy of the drug treatment was tested by assessing survival rate, fungal burden, and histological analysis in lung tissues. The safety of the drug formulations was tested by investigating hepatic, renal function, and antioxidant levels. The results of the present work demonstrated that Lip-EA, not FLZ, effectively eliminated <i>C. neoformans</i> infection in the leukopenic mice. Mice treated with Lip-EA (40 mg/kg) showed 70% survival rate and highly reduced fungal burden in their lung tissues, whereas the mice treated with FLZ (40 mg/kg) had 20% survival rate and greater fungal load in their lungs. Noteworthy, Lip-EA treatment alleviated cyclophosphamide-induced toxicity and restored hepatic and renal function parameters. Moreover, Lip-EA treatment restored the levels of superoxide dismutase and reduced glutathione and catalase in the lung tissues. The effect of FLZ or EA or Lip-EA against <i>C. neoformans</i> infection was assessed by the histological analysis of lung tissues. Lip-EA effectively reduced influx of inflammatory cells, thickening of alveolar walls, congestion, and hemorrhage. The findings of the present study suggest that Lip-EA may prove to be a promising therapeutic formulation against <i>C. neoformans</i> in immunocompromised persons. |
| first_indexed | 2024-03-10T10:24:49Z |
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| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T10:24:49Z |
| publishDate | 2021-06-01 |
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| spelling | doaj.art-cd2f14299b9b40e1ab4c84ba8e15bd8d2023-11-22T00:08:44ZengMDPI AGPharmaceutics1999-49232021-06-0113688210.3390/pharmaceutics13060882Liposomal Ellagic Acid Alleviates Cyclophosphamide-Induced Toxicity and Eliminates the Systemic <i>Cryptococcus neoformans</i> Infection in Leukopenic MiceMasood Alam Khan0Arif Khan1Mohd Azam2Khaled S. Allemailem3Faris Alrumaihi4Ahmad Almatroudi5Fahad A. Alhumaydhi6Faizul Azam7Shaheer Hasan Khan8Syeda Fauzia Farheen Zofair9Sumbul Ahmad10Hina Younus11Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi ArabiaDepartment of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi ArabiaDepartment of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi ArabiaDepartment of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi ArabiaDepartment of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi ArabiaDepartment of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi ArabiaDepartment of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi ArabiaDepartment of Pharmaceutical Chemistry & Pharmacognosy, Unaizah College of Pharmacy, Qassim University, Buraydah 51452, Saudi ArabiaInterdisciplinary Biotechnology Unit, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, IndiaInterdisciplinary Biotechnology Unit, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, IndiaInterdisciplinary Biotechnology Unit, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, IndiaInterdisciplinary Biotechnology Unit, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, India<i>Cryptococcus neoformans</i> infections rose sharply due to rapid increase in the numbers of immunocompromised individuals in recent years. Treatment of Cryptococcosis in immunocompromised persons is largely very challenging and hopeless. Hence, this study aimed to determine the activity of ellagic acid (EA) in the treatment of <i>C. neoformans</i> in cyclophosphamide injected leukopenic mice. A liposomal formulation of ellagic acid (Lip-EA) was prepared and characterized, and its antifungal activity was assessed in comparison to fluconazole (FLZ). The efficacy of the drug treatment was tested by assessing survival rate, fungal burden, and histological analysis in lung tissues. The safety of the drug formulations was tested by investigating hepatic, renal function, and antioxidant levels. The results of the present work demonstrated that Lip-EA, not FLZ, effectively eliminated <i>C. neoformans</i> infection in the leukopenic mice. Mice treated with Lip-EA (40 mg/kg) showed 70% survival rate and highly reduced fungal burden in their lung tissues, whereas the mice treated with FLZ (40 mg/kg) had 20% survival rate and greater fungal load in their lungs. Noteworthy, Lip-EA treatment alleviated cyclophosphamide-induced toxicity and restored hepatic and renal function parameters. Moreover, Lip-EA treatment restored the levels of superoxide dismutase and reduced glutathione and catalase in the lung tissues. The effect of FLZ or EA or Lip-EA against <i>C. neoformans</i> infection was assessed by the histological analysis of lung tissues. Lip-EA effectively reduced influx of inflammatory cells, thickening of alveolar walls, congestion, and hemorrhage. The findings of the present study suggest that Lip-EA may prove to be a promising therapeutic formulation against <i>C. neoformans</i> in immunocompromised persons.https://www.mdpi.com/1999-4923/13/6/882<i>C. neoformans</i>fluconazoleellagic acidliposomesleukopenia |
| spellingShingle | Masood Alam Khan Arif Khan Mohd Azam Khaled S. Allemailem Faris Alrumaihi Ahmad Almatroudi Fahad A. Alhumaydhi Faizul Azam Shaheer Hasan Khan Syeda Fauzia Farheen Zofair Sumbul Ahmad Hina Younus Liposomal Ellagic Acid Alleviates Cyclophosphamide-Induced Toxicity and Eliminates the Systemic <i>Cryptococcus neoformans</i> Infection in Leukopenic Mice Pharmaceutics <i>C. neoformans</i> fluconazole ellagic acid liposomes leukopenia |
| title | Liposomal Ellagic Acid Alleviates Cyclophosphamide-Induced Toxicity and Eliminates the Systemic <i>Cryptococcus neoformans</i> Infection in Leukopenic Mice |
| title_full | Liposomal Ellagic Acid Alleviates Cyclophosphamide-Induced Toxicity and Eliminates the Systemic <i>Cryptococcus neoformans</i> Infection in Leukopenic Mice |
| title_fullStr | Liposomal Ellagic Acid Alleviates Cyclophosphamide-Induced Toxicity and Eliminates the Systemic <i>Cryptococcus neoformans</i> Infection in Leukopenic Mice |
| title_full_unstemmed | Liposomal Ellagic Acid Alleviates Cyclophosphamide-Induced Toxicity and Eliminates the Systemic <i>Cryptococcus neoformans</i> Infection in Leukopenic Mice |
| title_short | Liposomal Ellagic Acid Alleviates Cyclophosphamide-Induced Toxicity and Eliminates the Systemic <i>Cryptococcus neoformans</i> Infection in Leukopenic Mice |
| title_sort | liposomal ellagic acid alleviates cyclophosphamide induced toxicity and eliminates the systemic i cryptococcus neoformans i infection in leukopenic mice |
| topic | <i>C. neoformans</i> fluconazole ellagic acid liposomes leukopenia |
| url | https://www.mdpi.com/1999-4923/13/6/882 |
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