Dose–response evaluation of cannabichromene on hepato-renal enzyme and non-enzyme biomarkers: the pharmacological controlled study
Cannabichromene (CBC) is one of the non-psychoactive cannabinoids found in Cannabis sativa and the second most abundant after cannabidiol. CBC has been shown to produce antinociception and anti-inflammatory effects in rodents; it is a major non-psychotropic phytocannabinoid that inhibits endocannabi...
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description | Cannabichromene (CBC) is one of the non-psychoactive cannabinoids found in
Cannabis sativa
and the second most abundant after cannabidiol. CBC has been shown to produce antinociception and anti-inflammatory effects in rodents; it is a major non-psychotropic phytocannabinoid that inhibits endocannabinoid inactivation and activates the transient receptor potential ankyrin-1 (TRPA1). The use of non-psychoactive cannabinoids as protective, ameliorative, and preventive agents in diverse disease pathophysiology is increasingly gaining global significance. Cannabidiol (CBD) has been extensively studied in this regard; however, CBC may also possess undiscovered intriguing and appreciable therapeutic properties. Therefore, the effects of 7 days of oral daily administration of 5 mg/kg,10 mg/kg, and 20 mg/kg body weight doses of CBC on antioxidant enzyme system, hepatic, and renal function biomarkers were investigated in this study. Twenty-four (24) male Wistar rats were divided into four groups of 6 animals each (1 control and 3 test groups). Twenty-four hours after the last treatment, the animals were anaesthetized using ketamine/xylazine and then euthanized via cervical dislocation. The liver and kidney were excised, while plasma and red blood cells were processed from the whole blood and used for biochemical analysis. Statistical analysis was done using one-way analysis of variance (ANOVA) with the Tukey’s test of homogeneity where appropriate;
p
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doi_str_mv | 10.1007/s00580-023-03491-0 |
format | Article |
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Cannabis sativa
and the second most abundant after cannabidiol. CBC has been shown to produce antinociception and anti-inflammatory effects in rodents; it is a major non-psychotropic phytocannabinoid that inhibits endocannabinoid inactivation and activates the transient receptor potential ankyrin-1 (TRPA1). The use of non-psychoactive cannabinoids as protective, ameliorative, and preventive agents in diverse disease pathophysiology is increasingly gaining global significance. Cannabidiol (CBD) has been extensively studied in this regard; however, CBC may also possess undiscovered intriguing and appreciable therapeutic properties. Therefore, the effects of 7 days of oral daily administration of 5 mg/kg,10 mg/kg, and 20 mg/kg body weight doses of CBC on antioxidant enzyme system, hepatic, and renal function biomarkers were investigated in this study. Twenty-four (24) male Wistar rats were divided into four groups of 6 animals each (1 control and 3 test groups). Twenty-four hours after the last treatment, the animals were anaesthetized using ketamine/xylazine and then euthanized via cervical dislocation. The liver and kidney were excised, while plasma and red blood cells were processed from the whole blood and used for biochemical analysis. Statistical analysis was done using one-way analysis of variance (ANOVA) with the Tukey’s test of homogeneity where appropriate;
p
< 0.05 was considered statistically significant. The activities of all antioxidant enzymes (catalase, CAT; superoxide dismutase, SOD; and glutathione peroxidase, GPx) were significantly (
p
< 0.05) increased in the liver, kidney, red blood cell, and plasma at all doses, especially at the 10 mg/kg body weight dose. The levels of non-enzymatic antioxidants (reduced glutathione, GSH; and nitric oxide, NO) were not significantly (
p
> 0.05) different at all exposed CBC doses. However, the malondialdehyde level (MDA) was increased notably in the kidney and plasma in the 10 mg/kg group. Hepatic function enzymes: aspartate transaminase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) activities were significantly decreased at the 10-mg/kg dose, although renal function markers seemed consistent at all the doses investigated. Histological evaluations of the kidney and liver revealed severe multifocal necrotizing tubule, interstitial nephritis, and degeneration of renal tubules and periportal hepatocellular necrosis with inflammation of the hepatocytes. Our study revealed modulation of the hepato-renal system via CBC exposure, and despite few reports of beneficial applications, we recommend caution in its use.</description><identifier>ISSN: 1618-565X</identifier><identifier>ISSN: 1618-5641</identifier><identifier>EISSN: 1618-565X</identifier><identifier>DOI: 10.1007/s00580-023-03491-0</identifier><language>eng</language><publisher>London: Springer London</publisher><subject>Alanine transaminase ; Alkaline phosphatase ; analysis of variance ; Ankyrins ; antioxidant enzymes ; Antioxidants ; Aspartate transaminase ; Biochemical analysis ; Biomarkers ; Blood ; Body weight ; Cannabidiol ; Cannabinoids ; Cannabis ; Cannabis sativa ; catalase ; cervical dislocation ; dose response ; Enzymes ; Erythrocytes ; glutathione ; Glutathione peroxidase ; Hematology ; Hepatocytes ; histology ; Inflammation ; Ketamine ; kidneys ; Liver ; liver function ; males ; malondialdehyde ; Medicine ; Medicine & Public Health ; necrosis ; Nephritis ; Nitric oxide ; Oncology ; Original Article ; Pain perception ; Pathology ; Pathophysiology ; Renal function ; Renal tubules ; Statistical analysis ; superoxide dismutase ; therapeutics ; Transient receptor potential proteins ; Variance analysis ; xylazine</subject><ispartof>Comparative clinical pathology, 2023-10, Vol.32 (5), p.811-826</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2180-bbeb7f3c3b332c62cd9317f5aa55606906ba7e0b4c1535dc7fbe0d67df4f87173</cites><orcidid>0000-0001-8752-3290</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00580-023-03491-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00580-023-03491-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids></links><search><creatorcontrib>Taiwo, Odunayo Anthonia</creatorcontrib><creatorcontrib>Dosumu, Oluwatosin Adebisi</creatorcontrib><creatorcontrib>Ajagbe, Nathaniel</creatorcontrib><creatorcontrib>Uwaogu, Cynthia</creatorcontrib><creatorcontrib>Ugwor, Emmanuel Ifeanyichukwu</creatorcontrib><creatorcontrib>James, Adewale Segun</creatorcontrib><title>Dose–response evaluation of cannabichromene on hepato-renal enzyme and non-enzyme biomarkers: the pharmacological controlled study</title><title>Comparative clinical pathology</title><addtitle>Comp Clin Pathol</addtitle><description>Cannabichromene (CBC) is one of the non-psychoactive cannabinoids found in
Cannabis sativa
and the second most abundant after cannabidiol. CBC has been shown to produce antinociception and anti-inflammatory effects in rodents; it is a major non-psychotropic phytocannabinoid that inhibits endocannabinoid inactivation and activates the transient receptor potential ankyrin-1 (TRPA1). The use of non-psychoactive cannabinoids as protective, ameliorative, and preventive agents in diverse disease pathophysiology is increasingly gaining global significance. Cannabidiol (CBD) has been extensively studied in this regard; however, CBC may also possess undiscovered intriguing and appreciable therapeutic properties. Therefore, the effects of 7 days of oral daily administration of 5 mg/kg,10 mg/kg, and 20 mg/kg body weight doses of CBC on antioxidant enzyme system, hepatic, and renal function biomarkers were investigated in this study. Twenty-four (24) male Wistar rats were divided into four groups of 6 animals each (1 control and 3 test groups). Twenty-four hours after the last treatment, the animals were anaesthetized using ketamine/xylazine and then euthanized via cervical dislocation. The liver and kidney were excised, while plasma and red blood cells were processed from the whole blood and used for biochemical analysis. Statistical analysis was done using one-way analysis of variance (ANOVA) with the Tukey’s test of homogeneity where appropriate;
p
< 0.05 was considered statistically significant. The activities of all antioxidant enzymes (catalase, CAT; superoxide dismutase, SOD; and glutathione peroxidase, GPx) were significantly (
p
< 0.05) increased in the liver, kidney, red blood cell, and plasma at all doses, especially at the 10 mg/kg body weight dose. The levels of non-enzymatic antioxidants (reduced glutathione, GSH; and nitric oxide, NO) were not significantly (
p
> 0.05) different at all exposed CBC doses. However, the malondialdehyde level (MDA) was increased notably in the kidney and plasma in the 10 mg/kg group. Hepatic function enzymes: aspartate transaminase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) activities were significantly decreased at the 10-mg/kg dose, although renal function markers seemed consistent at all the doses investigated. Histological evaluations of the kidney and liver revealed severe multifocal necrotizing tubule, interstitial nephritis, and degeneration of renal tubules and periportal hepatocellular necrosis with inflammation of the hepatocytes. Our study revealed modulation of the hepato-renal system via CBC exposure, and despite few reports of beneficial applications, we recommend caution in its use.</description><subject>Alanine transaminase</subject><subject>Alkaline phosphatase</subject><subject>analysis of variance</subject><subject>Ankyrins</subject><subject>antioxidant enzymes</subject><subject>Antioxidants</subject><subject>Aspartate transaminase</subject><subject>Biochemical analysis</subject><subject>Biomarkers</subject><subject>Blood</subject><subject>Body weight</subject><subject>Cannabidiol</subject><subject>Cannabinoids</subject><subject>Cannabis</subject><subject>Cannabis sativa</subject><subject>catalase</subject><subject>cervical dislocation</subject><subject>dose response</subject><subject>Enzymes</subject><subject>Erythrocytes</subject><subject>glutathione</subject><subject>Glutathione peroxidase</subject><subject>Hematology</subject><subject>Hepatocytes</subject><subject>histology</subject><subject>Inflammation</subject><subject>Ketamine</subject><subject>kidneys</subject><subject>Liver</subject><subject>liver function</subject><subject>males</subject><subject>malondialdehyde</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>necrosis</subject><subject>Nephritis</subject><subject>Nitric oxide</subject><subject>Oncology</subject><subject>Original Article</subject><subject>Pain perception</subject><subject>Pathology</subject><subject>Pathophysiology</subject><subject>Renal function</subject><subject>Renal tubules</subject><subject>Statistical analysis</subject><subject>superoxide dismutase</subject><subject>therapeutics</subject><subject>Transient receptor potential proteins</subject><subject>Variance analysis</subject><subject>xylazine</subject><issn>1618-565X</issn><issn>1618-5641</issn><issn>1618-565X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNp9kc1KxDAUhYMoqKMv4Crgxk01aSZJx534DwNuFNyFJL2d6dgmNWmFceXCN_ANfRKjIygu3Nw_vnPhcBDao-SQEiKPIiG8IBnJWUbYeEIzsoa2qKBFxgW_X_81b6LtGBeEUF4wtoVez3yE95e3ALHzLgKGJ90Muq-9w77CVjunTW3nwbfgAKfrHDrd-yyA0w0G97xsAWtXYudd9r2a2rc6PECIx7ifA-7mOrTa-sbPaptU1rs--KaBEsd-KJc7aKPSTYTd7z5Cdxfnt6dX2fTm8vr0ZJrZnCZ3xoCRFbPMMJZbkdtywqisuNacCyImRBgtgZixpZzx0srKACmFLKtxVUgq2QgdrP52wT8OEHvV1tFC02gHfoiKJZ0s2DgXCd3_gy78EJLlqPJCcsHEJKeJyleUDT7GAJXqQp2sLxUl6jMYtQpGpWDUVzCpjhBbiWKC3QzCz-t_VB-W8JTP</recordid><startdate>20231001</startdate><enddate>20231001</enddate><creator>Taiwo, Odunayo Anthonia</creator><creator>Dosumu, Oluwatosin Adebisi</creator><creator>Ajagbe, Nathaniel</creator><creator>Uwaogu, Cynthia</creator><creator>Ugwor, Emmanuel 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biomarkers: the pharmacological controlled study</title><author>Taiwo, Odunayo Anthonia ; Dosumu, Oluwatosin Adebisi ; Ajagbe, Nathaniel ; Uwaogu, Cynthia ; Ugwor, Emmanuel Ifeanyichukwu ; James, Adewale Segun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2180-bbeb7f3c3b332c62cd9317f5aa55606906ba7e0b4c1535dc7fbe0d67df4f87173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Alanine transaminase</topic><topic>Alkaline phosphatase</topic><topic>analysis of variance</topic><topic>Ankyrins</topic><topic>antioxidant enzymes</topic><topic>Antioxidants</topic><topic>Aspartate transaminase</topic><topic>Biochemical analysis</topic><topic>Biomarkers</topic><topic>Blood</topic><topic>Body weight</topic><topic>Cannabidiol</topic><topic>Cannabinoids</topic><topic>Cannabis</topic><topic>Cannabis sativa</topic><topic>catalase</topic><topic>cervical dislocation</topic><topic>dose response</topic><topic>Enzymes</topic><topic>Erythrocytes</topic><topic>glutathione</topic><topic>Glutathione peroxidase</topic><topic>Hematology</topic><topic>Hepatocytes</topic><topic>histology</topic><topic>Inflammation</topic><topic>Ketamine</topic><topic>kidneys</topic><topic>Liver</topic><topic>liver function</topic><topic>males</topic><topic>malondialdehyde</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>necrosis</topic><topic>Nephritis</topic><topic>Nitric oxide</topic><topic>Oncology</topic><topic>Original Article</topic><topic>Pain perception</topic><topic>Pathology</topic><topic>Pathophysiology</topic><topic>Renal function</topic><topic>Renal tubules</topic><topic>Statistical analysis</topic><topic>superoxide dismutase</topic><topic>therapeutics</topic><topic>Transient receptor potential proteins</topic><topic>Variance analysis</topic><topic>xylazine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Taiwo, Odunayo Anthonia</creatorcontrib><creatorcontrib>Dosumu, Oluwatosin Adebisi</creatorcontrib><creatorcontrib>Ajagbe, Nathaniel</creatorcontrib><creatorcontrib>Uwaogu, Cynthia</creatorcontrib><creatorcontrib>Ugwor, Emmanuel Ifeanyichukwu</creatorcontrib><creatorcontrib>James, Adewale Segun</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest 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Ifeanyichukwu</au><au>James, Adewale Segun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dose–response evaluation of cannabichromene on hepato-renal enzyme and non-enzyme biomarkers: the pharmacological controlled study</atitle><jtitle>Comparative clinical pathology</jtitle><stitle>Comp Clin Pathol</stitle><date>2023-10-01</date><risdate>2023</risdate><volume>32</volume><issue>5</issue><spage>811</spage><epage>826</epage><pages>811-826</pages><issn>1618-565X</issn><issn>1618-5641</issn><eissn>1618-565X</eissn><abstract>Cannabichromene (CBC) is one of the non-psychoactive cannabinoids found in
Cannabis sativa
and the second most abundant after cannabidiol. CBC has been shown to produce antinociception and anti-inflammatory effects in rodents; it is a major non-psychotropic phytocannabinoid that inhibits endocannabinoid inactivation and activates the transient receptor potential ankyrin-1 (TRPA1). The use of non-psychoactive cannabinoids as protective, ameliorative, and preventive agents in diverse disease pathophysiology is increasingly gaining global significance. Cannabidiol (CBD) has been extensively studied in this regard; however, CBC may also possess undiscovered intriguing and appreciable therapeutic properties. Therefore, the effects of 7 days of oral daily administration of 5 mg/kg,10 mg/kg, and 20 mg/kg body weight doses of CBC on antioxidant enzyme system, hepatic, and renal function biomarkers were investigated in this study. Twenty-four (24) male Wistar rats were divided into four groups of 6 animals each (1 control and 3 test groups). Twenty-four hours after the last treatment, the animals were anaesthetized using ketamine/xylazine and then euthanized via cervical dislocation. The liver and kidney were excised, while plasma and red blood cells were processed from the whole blood and used for biochemical analysis. Statistical analysis was done using one-way analysis of variance (ANOVA) with the Tukey’s test of homogeneity where appropriate;
p
< 0.05 was considered statistically significant. The activities of all antioxidant enzymes (catalase, CAT; superoxide dismutase, SOD; and glutathione peroxidase, GPx) were significantly (
p
< 0.05) increased in the liver, kidney, red blood cell, and plasma at all doses, especially at the 10 mg/kg body weight dose. The levels of non-enzymatic antioxidants (reduced glutathione, GSH; and nitric oxide, NO) were not significantly (
p
> 0.05) different at all exposed CBC doses. However, the malondialdehyde level (MDA) was increased notably in the kidney and plasma in the 10 mg/kg group. Hepatic function enzymes: aspartate transaminase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) activities were significantly decreased at the 10-mg/kg dose, although renal function markers seemed consistent at all the doses investigated. Histological evaluations of the kidney and liver revealed severe multifocal necrotizing tubule, interstitial nephritis, and degeneration of renal tubules and periportal hepatocellular necrosis with inflammation of the hepatocytes. Our study revealed modulation of the hepato-renal system via CBC exposure, and despite few reports of beneficial applications, we recommend caution in its use.</abstract><cop>London</cop><pub>Springer London</pub><doi>10.1007/s00580-023-03491-0</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0001-8752-3290</orcidid></addata></record> |
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subjects | Alanine transaminase Alkaline phosphatase analysis of variance Ankyrins antioxidant enzymes Antioxidants Aspartate transaminase Biochemical analysis Biomarkers Blood Body weight Cannabidiol Cannabinoids Cannabis Cannabis sativa catalase cervical dislocation dose response Enzymes Erythrocytes glutathione Glutathione peroxidase Hematology Hepatocytes histology Inflammation Ketamine kidneys Liver liver function males malondialdehyde Medicine Medicine & Public Health necrosis Nephritis Nitric oxide Oncology Original Article Pain perception Pathology Pathophysiology Renal function Renal tubules Statistical analysis superoxide dismutase therapeutics Transient receptor potential proteins Variance analysis xylazine |
title | Dose–response evaluation of cannabichromene on hepato-renal enzyme and non-enzyme biomarkers: the pharmacological controlled study |
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