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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Veröffentlicht in:Comparative clinical pathology 2023-10, Vol.32 (5), p.811-826
Hauptverfasser: Taiwo, Odunayo Anthonia, Dosumu, Oluwatosin Adebisi, Ajagbe, Nathaniel, Uwaogu, Cynthia, Ugwor, Emmanuel Ifeanyichukwu, James, Adewale Segun
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container_title Comparative clinical pathology
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creator Taiwo, Odunayo Anthonia
Dosumu, Oluwatosin Adebisi
Ajagbe, Nathaniel
Uwaogu, Cynthia
Ugwor, Emmanuel Ifeanyichukwu
James, Adewale Segun
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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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  &lt; 0.05 was considered statistically significant. The activities of all antioxidant enzymes (catalase, CAT; superoxide dismutase, SOD; and glutathione peroxidase, GPx) were significantly ( p  &lt; 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  &gt; 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. 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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). 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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 &amp; 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 Ifeanyichukwu</creator><creator>James, Adewale Segun</creator><general>Springer London</general><general>Springer Nature B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7S9</scope><scope>L.6</scope><orcidid>https://orcid.org/0000-0001-8752-3290</orcidid></search><sort><creationdate>20231001</creationdate><title>Dose–response evaluation of cannabichromene on hepato-renal enzyme and non-enzyme biomarkers: the pharmacological controlled study</title><author>Taiwo, Odunayo Anthonia ; 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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 &amp; 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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  &lt; 0.05 was considered statistically significant. The activities of all antioxidant enzymes (catalase, CAT; superoxide dismutase, SOD; and glutathione peroxidase, GPx) were significantly ( p  &lt; 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  &gt; 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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