Category Archives: Kidney Disease

The Identification of Novel Anti-Inflammatory Effects of Cannabigerol in the Kidney Tissue of Rats Subjected to a High-Fat High-Sucrose Diet

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“The inflammatory state is a significant factor associated with diabetic kidney disease (DKD), making it one of the significant causes of chronic kidney disease. Despite the availability of data, there is a lack of targeted treatment strategies for diabetes-related kidney disorders.

The aim of our study was to determine the impact of cannabigerol (CBG) on lipid precursors for inflammatory mediators during DKD development.

A six-week experiment was conducted on male Wistar rats fed standard (Control) or high-fat high-sucrose (HFHS) diets. For the last 14 days of the experiment (5th and 6th weeks), half of the rats from the Control and HFHS groups intragastrically received CBG solution. Gas-liquid chromatography (GLC) was used to measure the activities of n-6 and n-3 polyunsaturated fatty acid (PUFA) metabolic pathways and the concentrations of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) in selected lipid fractions. Immunoblotting was performed to assess the expression of proteins involved in the regulation of the inflammatory state. A multiplex immunoassay kit was used to determine kidney toxicity biomarker levels.

Our results revealed that CBG administration to rats fed an HFHS diet decreased n-6 PUFA biosynthetic pathway activity in phospholipid (PL) and triacylglycerol (TAG) and increased n-3 PUFA biosynthetic pathway activity in TAG and free fatty acid (FFA). We also observed a reduction in the AA concentration in PL, FFA, and diacylglycerol (DAG). CBG supplementation reduced the level of kidney damage biomarkers, such as osteopontin (OPN).

Our observations confirm that CBG has potential anti-inflammatory properties and may be successfully used for further research to seek targeted therapies of inflammatory disorders, including diabetic kidney disease progression.”

https://pubmed.ncbi.nlm.nih.gov/40243749/

“These results suggest that cannabigerol may have potential anti-inflammatory effects and could be used as a therapeutic agent to support the treatment of inflammatory-related diseases.”

https://www.mdpi.com/1422-0067/26/7/3114

Lebanese cannabis oil extract protected against folic acid-induced kidney fibrosis in rats

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“Background: Renal fibrosis is a major manifestation of chronic kidney disease. To date, there are no treatments to reverse kidney fibrosis. Cannabis is an aromatic herb that is widely known for its anti-diabetic and anti-inflammatory properties. The aim of this study is to evaluate the protective effect of Lebanese cannabis oil extract (COE) against folic acid (FA) induced renal injury both in vitro and in vivo.

Materials and methods: A single dose of 250 mg/kg of Folic acid was administered to induce renal fibrosis in rats. COE was injected at varying doses of 5, 10, and 20 mg/kg. Body weight of rats were monitored and clinical parameters including serum creatinine, urea, and electrolytes were measured. Moreover, pathological examination of the kidney and heart was performed. Conditionally immortalized cultured rat podocytes were exposed to high concentrations of folic acid in the presence or absence of COE. MTS and in vitro scratch assay were used to assess podocyte cells viability and migration respectively. Western blot analysis was used to evaluate the phosphorylation levels of AKT and p38 MAPK.

Results: Rats that received FA showed a marked increase in serum creatinine when compared to the non-treated control group. COE at doses of 5 and 10 mg/kg significantly decreased serum creatinine induced by FA. Serum sodium was significantly reduced in all the groups receiving COE. Furthermore, COE ameliorated renal and cardiac pathology abnormalities caused by FA in a dose-dependent manner. Cell viability assay revealed that COE reversed cytotoxicity induced by FA in rat podocytes. In vitro scratch assay showed that COE partially restored the migratory capacity of podocytes incubated with FA. Dose-dependent experiments showed that COE (1 and 2μg/ml) induced a significant increase of phospho-(S473)-AKT along with a decrease in phospho (T180 + Y182) P38 levels.

Conclusion: The current results revealed important protective effect of Lebanese cannabis oil extract against folic acid-induced renal fibrosis in rats.”

https://pubmed.ncbi.nlm.nih.gov/39666622/

“The current findings demonstrated that COE was able to significantly reduced serum creatinine in rat model of FA—induced nephrotoxicity. The beneficial effect COE was also evident in kidney and cardiac pathology examination. Furthermore, COE showed promise as a preventive and therapeutic treatment against FA-induced nephrotoxicity. “

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0311790

Cannabidiol attenuates arsenic-induced nephrotoxicity via the NOX4 and NF-κB pathways in mice

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“Background and purpose: Cannabidiol (CBD) is a phenolic terpene compound with anticancer, antioxidant, anti-inflammatory, antibacterial, neuroprotective, and anticonvulsant properties. Since the effects of CBD on sodium arsenite (As)-induced nephrotoxicity have not been fully determined, this study investigated the effect of CBD on As-induced nephrotoxicity by evaluating the NOX4 and NF-kB pathways in mice.

Experimental approach: 48 male mice were divided into six groups (8 each) including group 1, receiving saline for 14 days; group 2, receiving CBD (10 mg/kg, intraperitoneally) from the 7th to the 14th day; group 3, receiving As (10 mg/kg) for 14 days by gavage; and treatment groups 4-6, receiving CBD (2.5, 5, and 10 mg/kg, i.p.) 1.5 h before As (10 mg/kg by gavage, for 14 days) from the 7th to the 14th day. Mice were anesthetized after overnight fasting on day 15, and the blood sample was collected from their hearts. The level of antioxidants and pro-inflammatory factors, the expression of ROS and TNF-α, NF-kB, NOX4, iNOS, cleaved PARP, and caspase-3 proteins were measured and histological studies were performed.

Findings/results: Exposure to As significantly increased kidney markers, oxidative stress, apoptosis, and inflammation in mice kidney tissue, and pretreatment with CBD reversed these changes. In addition, CBD significantly decreased the expression of NF-kB and NOX4, and the levels of pro-inflammatory factors and the expression of cleaved PARP and increased the level of antioxidants.

Conclusion and implications: CBD ameliorated As-induced nephrotoxicity related to inhibiting oxidative stress, inflammation, and apoptosis, potentially through the NF-kB/Nox4 pathway.”

https://pubmed.ncbi.nlm.nih.gov/39399730/

“This study confirmed that CBD attenuates As-induced nephrotoxicity in mice. CBD led to the strengthening of antioxidant defense, reduction of lipid peroxidation, inflammation and expression of proteins of NF-kB, NOX4, iNOS, cleaved PARP, and caspase-3. The dose of 10 mg/kg of CBD showed better results than 5, and 2.5 mg/kg. Finally, the findings of the present study provide evidence that CBD may serve as a potential therapeutic agent for the prevention and treatment of arsenic-induced nephrotoxicity. “

https://journals.lww.com/rips/fulltext/2024/19040/cannabidiol_attenuates_arsenic_induced.8.aspx

Chronic cannabidiol treatment induces cardiovascular improvement in renovascular hypertensive rats

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“Background: Cannabidiol (CBD) is increasingly studied for its therapeutic potential in neurodegenerative diseases. Previous research on acute CBD administration has demonstrated cardiovascular benefits in hypertensive rats, including reduced mean blood pressure and oxidative stress.

Aim: To investigate the long-term cardiovascular effects of chronic CBD treatment in renovascular hypertension induced by the 2-kidney-1-clip (2K1C) model.

Methods: Male Wistar rats (180-200 g, 8 weeks old) underwent 2K1C or SHAM surgery. Six weeks later, rats received chronic CBD treatment (20 mg/kg, twice daily for 14 days). A combination of ex vivo, in vitro, and in vivo methods was used to assess CBD’s cardiovascular effects in 2K1C hypertensive rats.

Results: Chronic CBD treatment significantly reduced blood pressure and the depressor response to hexamethonium (a ganglionic blocker). It also normalized variability in low-frequency (LF) power and LF/high-frequency (HF) ratio. CBD enhanced vasodilation and reduced vasoconstriction in the mesenteric artery of 2K1C rats, accompanied by decreased expression of aortic reactive oxygen species (ROS).

Conclusion: Our findings suggest that chronic CBD treatment exerts antihypertensive effects by improving baroreflex sensitivity and vascular function while decreasing arterial ROS levels and sympathetic nerve activity. These results underscore CBD’s potential therapeutic role in managing cardiovascular complications associated with renovascular hypertension.”

https://pubmed.ncbi.nlm.nih.gov/39351852/

https://journals.lww.com/jhypertension/abstract/9900/chronic_cannabidiol_treatment_induces.554.aspx

Cannabis-Containing Cream for CKD-Associated Pruritus: A Double-Blind, Placebo Controlled Trial

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“Rationale & objective: This study aims to compare the efficacy of a cannabis cream and a placebo in the treatment of chronic kidney disease (CKD)-associated pruritus.

Study design: A double-blind randomized controlled study.

Setting & participants: Sixty hemodialysis patients with the worst itching intensity numerical rating scale (WI-NRS) ≥3.

Exposure: Patients received cannabis cream or placebo.

Outcomes: The primary endpoint was the WI-NRS score at week 4. The secondary endpoints included the WI-NRS at week 2, the Skindex-10 score at weeks 2 and 4, and the mean difference score between baseline and week 4 for the WI-NRS and the Skindex-10 score.

Analytical approach: We used unpaired t tests or Mann Whitney U tests, along with χ2 or Fisher exact tests as appropriate. The adjusted mean differences were determined using ANCOVA, adjusting for baseline scores.

Results: Among 60 participants, the mean age was 61.6 ± 14.4 years and the mean baseline WI-NRS was 6.7 ± 1.7. The placebo and cannabis cream groups were similar at baseline, although more individuals in the placebo group had diabetes. At 4 weeks, the WI-NRS dropped to 2.6 in the cannabis group and 3.6 in the placebo group (the mean difference after adjustment for baseline scores:-1.1, 95% CI, -2.1 to -0.2; P = 0.02). Skindex-10 scores at week 4 were also lower in the cannabis group, but after adjustment for baseline scores, statistical significance was not maintained. No side effects were observed in either group.

Limitations: A single study with a small sample size restricts its generalizability. Variances in participants’ diabetes statuses might have affected the itch outcomes. The absence of cannabinoid level assessment in blood prevents conclusive determination of the potential systemic impacts. A 4-week follow-up period inadequately captures long-term effect.

Conclusions: In CKD-associated pruritus, the topical cream containing cannabis significantly reduced the severity of itching symptoms compared to the placebo.”

https://pubmed.ncbi.nlm.nih.gov/39328960/

https://www.kidneymedicinejournal.org/article/S2590-0595(24)00105-5/fulltext

The renoprotective effects of cannabidiol on lipopolysaccharide-induced systemic inflammation model of rats

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“Sepsis-induced renal damage poses a significant threat, necessitating effective therapeutic strategies. Cannabidiol (CBD) has beneficial effects on tissues and their functions by exhibiting antioxidant and anti-inflammatory effects. This study investigates the potential protective effects of CBD in mitigating lipopolysaccharide (LPS)-induced renal injury in Wistar Albino rats.

Thirty-two Wistar Albino rats were categorized into control, LPS (5 mg/kg i.p.), LPS + CBD, and CBD (5 mg/kg i.p.) groups. After the experiment, samples were collected for biochemical, genetic, histopathological, and immunohistochemical analyses. Oxidative stress markers as total oxidant status (TOS) and total antioxidant status (TAS), oxidative stress index (OSI), superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), immune staining as tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10), caspase-3, gene expressions as nuclear factor erythroid 2-related factor 2 (NRF2), C/EBP homologous protein (CHOP), caspase-9, glucose-regulating protein 78 (GRP78), B-cell leukemia/lymphoma 2 (Bcl2), and tissue histology have been examined.

The LPS-exposed group exhibited significant renal abnormalities, mitigated by CBD intervention in the LPS + CBD group. CBD reduced immunoexpression scores for TNF-α, caspase-3, and IL-10. Biochemically, CBD induced a positive shift in the oxidative balance, increasing TAS, SOD, and GPx, while decreasing TOS, OSI, and MDA levels. Genetic analyses highlighted CBD’s regulatory impact on NRF2, CHOP, caspase-9, GRP78, and Bcl2, providing molecular insights into its protective role against LPS-induced renal damage.

This study underscores CBD as a promising protective agent against sepsis-induced renal damage. Our findings could provide valuable insights into potential therapeutic avenues for addressing renal complications in sepsis.”

https://pubmed.ncbi.nlm.nih.gov/39180672/

https://link.springer.com/article/10.1007/s00210-024-03391-2

Cannabigerolic Acid (CBGA) Inhibits the TRPM7 Ion Channel Through its Kinase Domain

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“Cannabinoids are a major class of compounds produced by the plant Cannabis sativa. Previous work has demonstrated that the main cannabinoids cannabidiol (CBD) and tetrahydrocannabinol (THC) can have some beneficial effects on pain, inflammation, epilepsy, and chemotherapy-induced nausea and vomiting. While CBD and THC represent the two major plant cannabinoids, some hemp varieties with enzymatic deficiencies produce mainly cannabigerolic acid (CBGA). We recently reported that CBGA has a potent inhibitory effect on both Store-Operated Calcium Entry (SOCE) via inhibition of Calcium Release-Activated Calcium (CRAC) channels as well as currents carried by the channel-kinase TRPM7. Importantly, CBGA prevented kidney damage and suppressed mRNA expression of inflammatory cytokines through inhibition of these mechanisms in an acute nephropathic mouse model. In the present study, we investigate the most common major and minor cannabinoids to determine their potential efficacy on TRPM7 channel function. We find that approximately half of the tested cannabinoids suppress TRPM7 currents to some degree, with CBGA having the strongest inhibitory effect on TRPM7. We determined that the CBGA-mediated inhibition of TRPM7 requires a functional kinase domain, is sensitized by both intracellular Mg⋅ATP and free Mg2+ and reduced by increases in intracellular Ca2+. Finally, we demonstrate that CBGA inhibits native TRPM7 channels in a B lymphocyte cell line. In conclusion, we demonstrate that CBGA is the most potent cannabinoid in suppressing TRPM7 activity and possesses therapeutic potential for diseases in which TRPM7 is known to play an important role such as cancer, stroke, and kidney disease.”

https://pubmed.ncbi.nlm.nih.gov/38162115/

https://academic.oup.com/function/article/5/1/zqad069/7462310?login=false

Prospective affirmative therapeutics of cannabidiol oil mitigates doxorubicin-induced abnormalities in kidney function, inflammation, and renal tissue changes

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“Nephropathy is the decline in kidney function. A promising treatment for numerous types of illness is using natural materials as natural chemical compounds. The inquiry was conducted to investigate cannabidiol (CBD) potential for renal syndrome protection. The five equal groups of fifty male Sprague-Dawley rats weighing 150 ± 25 g each were designed; group I received distilled water orally, while group II got an intraperitoneal injection of doxorubicin (18 mg/kg bwt). Group III received CBD (26 mg/kg bwt) orally, while group IV received 1 ml of CBD (26 mg/kg bwt) and group V received trimetazidine (10 mg/kg bwt), in addition to a single intraperitoneal dose of doxorubicin (18 mg/kg bwt) on the 11th day for both groups (IV, V). The administration of CBD (26 mg/kg bwt) led to a noticeable improvement in oxidative stress parameters (SOD and GSH) in rats by significantly lowering enzyme activity (ALT and AST), as well as serum creatinine and urea, IL-6, and MDA, confirming the anti-inflammatory accuracy of CBD linked to significant lowering to IL6R DNA frequency concentration in line with histopathology results. As a result of its anti-inflammatory and antioxidant capabilities, cannabidiol may have protective quality, and CBD medication could be related to controlling renal problems.”

https://pubmed.ncbi.nlm.nih.gov/37971510/

https://link.springer.com/article/10.1007/s00210-023-02836-4

CBGA ameliorates inflammation and fibrosis in nephropathy

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Scientific Reports

“Cannabidiol (CBD) is thought to have multiple biological effects, including the ability to attenuate inflammatory processes. Cannabigerols (CBGA and its decarboxylated CBG molecule) have pharmacological profiles similar to CBD. The endocannabinoid system has recently emerged to contribute to kidney disease, however, the therapeutic properties of cannabinoids in kidney disease remain largely unknown. In this study, we determined whether CBD and CBGA can attenuate kidney damage in an acute kidney disease model induced by the chemotherapeutic cisplatin. In addition, we evaluated the anti-fibrosis effects of these cannabinoids in a chronic kidney disease model induced by unilateral ureteral obstruction (UUO). We find that CBGA, but not CBD, protects the kidney from cisplatin-induced nephrotoxicity. CBGA also strongly suppressed mRNA of inflammatory cytokines in cisplatin-induced nephropathy, whereas CBD treatment was only partially effective. Furthermore, both CBGA and CBD treatment significantly reduced apoptosis through inhibition of caspase-3 activity. In UUO kidneys, both CBGA and CBD strongly reduced renal fibrosis. Finally, we find that CBGA, but not CBD, has a potent inhibitory effect on the channel-kinase TRPM7. We conclude that CBGA and CBD possess reno-protective properties, with CBGA having a higher efficacy, likely due to its dual anti-inflammatory and anti-fibrotic effects paired with TRPM7 inhibition.”

https://pubmed.ncbi.nlm.nih.gov/37072467/

“CBGA and CBD alone or in combination could be helpful as therapeutic options to treat chronic kidney disease with anti-inflammatory and anti-fibrotic properties and CBGA may be able to serve as an adjuvant for cisplatin chemotherapy.”

https://www.nature.com/articles/s41598-023-33507-2

A Retrospective Cohort Study That Examined the Impact of Cannabis Consumption on Long-Term Kidney Outcomes

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“Background: Cannabis consumption for recreational and medical use is increasing worldwide. However, the long-term effects on kidney health and disease are largely unknown. 

Materials and Methods: Post hoc analysis of cannabis use as a risk factor for kidney disease was performed using data from the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) study that enrolled hospitalized adults with and without acute kidney injury from four U.S. centers during 2009-2015. Associations between self-reported cannabis consumption and the categorical and continuous outcomes were determined using multivariable Cox regression and linear mixed models, respectively. 

Results: Over a mean follow-up of 4.5±1.8 years, 94 participants without chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] >60 mL/min/1.73 m2) who consumed cannabis had similar rates of annual eGFR decline versus 889 nonconsumers (mean difference=-0.02 mL/min/1.73 m2/year, p=0.9) and incident CKD (≥25% reduction in eGFR compared with the 3-month post-hospitalization measured eGFR and achieving CKD stage 3 or higher) (adjusted hazard ratio [aHR]=1.2; 95% confidence interval [CI]=0.7-2.0). Nineteen participants with CKD (eGFR <60 mL/min/1.73 m2) who consumed cannabis had more rapid eGFR decline versus 597 nonconsumers (mean difference=-1.3 mL/min/1.73 m2/year; p=0.02) that was not independently associated with an increased risk of CKD progression (≥50% reduction in eGFR compared with the 3-month post-hospitalization eGFR, reaching CKD stage 5, or receiving kidney replacement therapy) (aHR=1.6; 95% CI=0.7-3.5). Cannabis consumption was not associated with the rate of change in urine albumin to creatinine ratio (UACR) over time among those with (p=0.7) or without CKD (p=0.4). 

Conclusions: Cannabis consumption did not adversely affect the kidney function of participants without CKD but was associated with a faster annual eGFR decline among participants with CKD. Cannabis consumption was not associated with changes in UACR over time, incident CKD, or progressive CKD regardless of baseline kidney function. Additional research is needed to investigate the kidney endocannabinoid system and the impact of cannabis use on kidney disease outcomes.”

https://pubmed.ncbi.nlm.nih.gov/36791309/

https://www.liebertpub.com/doi/10.1089/can.2022.0141