TY - JOUR
T1 - Therapeutic Potential of Capsaicin against Cyclophosphamide-Induced Liver Damage
AU - Alam, Mohammad Firoz
AU - Ajeibi, Ahmed O.
AU - Safhi, Majed H.
AU - Alabdly, Ahmad J.A.
AU - Alshahrani, Saeed
AU - Rashid, Hina
AU - Qadri, Marwa
AU - Jali, Abdulmajeed M.
AU - Alqahtani, Saud
AU - Nomier, Yousra
AU - Moni, Sivakumar S.
AU - Khalid, Mohammad
AU - Anwer, Tarique
N1 - Funding Information:
The authors extend their appreciation to the Deputyship for Research and Innovation, Ministry of Education in Saudi Arabia for funding this research work through the project number ISP22-17.
Publisher Copyright:
© 2023 by the authors.
PY - 2023/1/24
Y1 - 2023/1/24
N2 - Cyclophosphamide (CPM) is a classical alkylating agent used in different cancer chemotherapy regimens and is restricted due to severe adverse effects, including hepatotoxicity. Natural or plant-derived antioxidants such as capsaicin were utilized in this study to examine the hepatoprotective benefits against cyclophosphamide-induced hepatotoxicity. The rats were divided into five groups: a normal control group, a toxic group (CPM), an intraperitoneal injection of a single dose of 200 mg/kg b.w. on the fourth day, a pretreated group with two doses of CPS (10 mg and 20 mg/kg b.w.) orally for six consecutive days, and an intraperitoneal administration of 200 mg/kg b.w. on the fourth day of treatment. The fifth group was administered with the highest dose of CPS (20 mg/kg b.w.) orally for six consecutive days. After 24 h of administration of CPS, the rats were anesthetized, blood was collected, and the serum enzyme toxicity was evaluated. After the blood sampling and euthanasia of all the animals, the liver was isolated for further toxicity and histopathological examination. The results revealed that serum liver markers (AST, ALT, ALP, BLI) significantly increased after CPM administration, but were subsequently restored after CPS treatment with both doses. In addition, lipid peroxidation (MDA), inflammatory cytokines (IL-1β, TNF-α), and apoptotic markers (Caspase-3) increased, and antioxidant enzymes (GSH, CAT, SOD) were significantly decreased after CPM administration, and it was re-established by CPS treatment. However, CPS effectively protected against the CPM-induced histopathological architects of liver tissues. In conclusion, CPS attenuates CPM-induced hepatotoxicity via modulating oxidative stress, apoptotic signals, and cytokine pathway. Therefore, CPS could play a significant role as a supplement during the chemotherapy of patients.
AB - Cyclophosphamide (CPM) is a classical alkylating agent used in different cancer chemotherapy regimens and is restricted due to severe adverse effects, including hepatotoxicity. Natural or plant-derived antioxidants such as capsaicin were utilized in this study to examine the hepatoprotective benefits against cyclophosphamide-induced hepatotoxicity. The rats were divided into five groups: a normal control group, a toxic group (CPM), an intraperitoneal injection of a single dose of 200 mg/kg b.w. on the fourth day, a pretreated group with two doses of CPS (10 mg and 20 mg/kg b.w.) orally for six consecutive days, and an intraperitoneal administration of 200 mg/kg b.w. on the fourth day of treatment. The fifth group was administered with the highest dose of CPS (20 mg/kg b.w.) orally for six consecutive days. After 24 h of administration of CPS, the rats were anesthetized, blood was collected, and the serum enzyme toxicity was evaluated. After the blood sampling and euthanasia of all the animals, the liver was isolated for further toxicity and histopathological examination. The results revealed that serum liver markers (AST, ALT, ALP, BLI) significantly increased after CPM administration, but were subsequently restored after CPS treatment with both doses. In addition, lipid peroxidation (MDA), inflammatory cytokines (IL-1β, TNF-α), and apoptotic markers (Caspase-3) increased, and antioxidant enzymes (GSH, CAT, SOD) were significantly decreased after CPM administration, and it was re-established by CPS treatment. However, CPS effectively protected against the CPM-induced histopathological architects of liver tissues. In conclusion, CPS attenuates CPM-induced hepatotoxicity via modulating oxidative stress, apoptotic signals, and cytokine pathway. Therefore, CPS could play a significant role as a supplement during the chemotherapy of patients.
KW - capsaicin
KW - cyclophosphamide
KW - hepatotoxicity
KW - histopathology
KW - inflammatory cytokines
KW - oxidative stress
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U2 - 10.3390/jcm12030911
DO - 10.3390/jcm12030911
M3 - Article
C2 - 36769559
AN - SCOPUS:85147888368
SN - 2077-0383
VL - 12
JO - Journal of Clinical Medicine
JF - Journal of Clinical Medicine
IS - 3
M1 - 911
ER -